Ignite Creation Date:
2025-12-24 @ 11:33 PM
Ignite Modification Date:
2026-03-19 @ 2:46 AM
Study NCT ID:
NCT02546856
Status:
COMPLETED
Last Update Posted:
2020-12-16
First Post:
2015-05-18
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'juanaoy@hotmail.com', 'phone': '34 656780945', 'title': 'Juana Oyanguren, Nursing graduate, Master in Heart Failure, CV Pathology and Thrombosis Specialist', 'organization': 'Servicio de Cardiologıa, Hospital Universitario Galdakao-Usansolo, OSI Barrualde-Galdakao-Osakidetza, Servicio Vasco de Salud, Galdakao, Bizkaia, Spain .BIOCRUCES, Instituto de Investigacion Sanitaria, Bizkaia, Spain'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'the implementation of ETIFIC in a single country; its recruitment characteristics, inclusion of de novo HF patients exclusively, relatively young patients and the low percentage of women and patients with ischemic heart disease.'}}, 'adverseEventsModule': {'timeFrame': 'From Baseline to 6 months', 'eventGroups': [{'id': 'EG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines', 'otherNumAtRisk': 145, 'deathsNumAtRisk': 145, 'otherNumAffected': 20, 'seriousNumAtRisk': 145, 'deathsNumAffected': 4, 'seriousNumAffected': 11}, {'id': 'EG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support', 'otherNumAtRisk': 144, 'deathsNumAtRisk': 144, 'otherNumAffected': 22, 'seriousNumAtRisk': 144, 'deathsNumAffected': 3, 'seriousNumAffected': 2}], 'otherEvents': [{'term': 'heart rate <50 bpm', 'notes': 'heart rate \\< 50 bpm, bradycardia possibly due to the titration process', 'stats': [{'groupId': 'EG000', 'numAtRisk': 145, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 144, 'numEvents': 10, 'numAffected': 10}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'symptomatic hypotension', 'notes': 'symptomatic hypotension possibly due to the titration process', 'stats': [{'groupId': 'EG000', 'numAtRisk': 145, 'numEvents': 13, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 144, 'numEvents': 12, 'numAffected': 12}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'hospitalizations due to cardiovascular cause', 'notes': 'unplanned hospitalizations due to cardiovascular cause (not due to non cardiovascular cause)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 145, 'numEvents': 11, 'numAffected': 11}, {'groupId': 'EG001', 'numAtRisk': 144, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'BB % Relative Dose (Mean) With Regard to Target Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" Left Ventricular ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" Left Ventricular ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" Left Ventricular ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" Left Ventricular ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" Left Ventricular ejection Fraction (EF) ≤ 40% Patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines.'}], 'classes': [{'categories': [{'measurements': [{'value': '56.29', 'spread': '31.3', 'groupId': 'OG000'}, {'value': '71.09', 'spread': '31.05', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '14.8', 'ciLowerLimit': '7.5', 'ciUpperLimit': '22.1', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'For the hypothesis that the relative dose of BBs would reach 52% by the end of the study and using an equivalence margin of 7%, we would need 157 patients per group for an alpha level of significance of 0.05 and a statistical power of 80% (beta of 0.80).'}], 'paramType': 'MEAN', 'timeFrame': '4 months', 'description': 'BB mean Relative dose is the mean dose of betablockers achieved 4 months after starting titration, relative to target dose ( %) , which is the target dose of european heart failure guidelines for BB.', 'unitOfMeasure': 'percentage of target dose', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Worsening Renal Function (From Baseline to 4th Month)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines.'}], 'classes': [{'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.52', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.4', 'ciLowerLimit': '-3.33', 'ciUpperLimit': '6.32', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of participants with worsening renal function during the titration process (from baseline to 4 month) that could be associated to the titration process (Creatinine increase \\>50% baseline creatinine or creatinine\\>3mg/dl, or Estimated Glomerular Filtration\\<25 ml/min/1.73 m2)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Potassium (K) ≥5.5 Meq/l (From Baseline to 4 Month)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.31', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '2.10', 'ciLowerLimit': '-1.9', 'ciUpperLimit': '6.1', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of participants with Potassium≥ 5.5 meq/l during the titration process (from baseline to 4 month) that could be associated to this titration process', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Symptomatic Hypotension (From Baseline to 4 Month)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '13', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.85', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.63', 'ciLowerLimit': '-7.1', 'ciUpperLimit': '5.85', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Description: Number of participants with symptomatic hypotension during the titration process (from baseline to 4 month) that could be associated to this titration process. Symptomatic hypotension defined as symptoms such as dizziness or light headedness, associated to hypotension', 'calculatePct': False, 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Heart Rate (HR) < 50 Beats Per Minute (From Baseline to 4 Month)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines with cardiologist prescription and support.\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.44', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '2.12', 'ciLowerLimit': '-3.3', 'ciUpperLimit': '7.54', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of participants with Heart Rate (HR) \\< 50 beats per minute during the titration process (from baseline to 4 month) , which could be associated to the titration process. (with or without symptoms)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Patients With Atrio Ventricular (AV) Block Due to Titration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients,. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of patients with AV Block during the titration process, associated to the BB titration', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Patients With Worsening of Heart Failure Signs and Symptoms', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients,. Protocol based on 2012 ESC HF guidelines.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.56', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.70', 'ciLowerLimit': '-1.6', 'ciUpperLimit': '3.04', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of patients with worsening of heart failure signs and symptoms during the titration process ( from baseline to 4 month) which could be associated to the titration process.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Patients With Admissions Due to Titration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patient. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of patients with admissions due to titration ( not due to other causes)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Patients: Mortality Due to Titration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'Number of patients: Mortality due to titration ( not due to other causes)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Paticipants With Drug Stop (Some Titration Drug Withdrawal Due to Intolerance, no Need or Change to Other Treatment)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients,. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'title': 'betablocker stop', 'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}, {'title': 'ACEI stop', 'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}, {'title': 'ARB stop', 'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}, {'title': 'MRA stop', 'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 months', 'description': 'number of paticipants with drug Stop ( withdrawal) that occur during the titration process that could be due to an adverse event. ( it can be not only due to an adverse event but because there is no need of this drug or its substitution for another kind of drug)', 'calculatePct': False, 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants analyzed are only participants with drug withdrawal'}, {'type': 'SECONDARY', 'title': 'Change in % Left Ventricular Ejection Fraction', 'denoms': [{'units': 'Participants', 'counts': [{'value': '138', 'groupId': 'OG000'}, {'value': '136', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '15.46', 'spread': '11.46', 'groupId': 'OG000'}, {'value': '15.63', 'spread': '13.29', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.96', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.07', 'ciLowerLimit': '-2.69', 'ciUpperLimit': '2.83', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': 'Change in % Left Ventricular Ejection Fraction (difference of change from baseline to 6 months between groups) Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts.', 'unitOfMeasure': 'percentage of blood expelled/each beat', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'It has to be taken into account that in outcome mesasures the order of groups and their number of participants is reversed ( first HF cardiologist, second HF nurse) in regard to those in the participant flow. ( first HF nurse, second HF cardiologist)'}, {'type': 'SECONDARY', 'title': 'N-terminal Pro-B Type Natriuretic Peptide Improvement (Nt-proBNP)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '121', 'groupId': 'OG000'}, {'value': '117', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines with cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '-1577', 'spread': '3225', 'groupId': 'OG000'}, {'value': '-1593', 'spread': '2733', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.97', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '16.47', 'ciLowerLimit': '-781', 'ciUpperLimit': '748', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': 'Nt-proBNP (N-terminal pro-B type natriuretic peptide) Improvement (Decrease) difference of change from baseline to 6 months between groups, mean (SD)', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'BNP was analysed in 11 patients of both groups, instead of Nt proBNP ( 121/117).'}, {'type': 'SECONDARY', 'title': '6 Minute Walking Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '138', 'groupId': 'OG000'}, {'value': '136', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '50.49', 'spread': '74.20', 'groupId': 'OG000'}, {'value': '57.76', 'spread': '79.97', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.44', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '7.28', 'ciLowerLimit': '-11.27', 'ciUpperLimit': '25.83', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': '6 minute walking test improvement ( change) meters.Improvement (difference of change from baseline to 6 months between groups Six minute walking test. Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. It provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. The six-minute walk test (6MWT) measures the distance (meters) an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway.', 'unitOfMeasure': 'meters', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants n(%) in New York Heart Association Functional Classification I,II,III,IV', 'denoms': [{'units': 'Participants', 'counts': [{'value': '137', 'groupId': 'OG000'}, {'value': '135', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'title': 'NYHA I', 'measurements': [{'value': '47', 'groupId': 'OG000'}, {'value': '59', 'groupId': 'OG001'}]}, {'title': 'NYHA II', 'measurements': [{'value': '86', 'groupId': 'OG000'}, {'value': '72', 'groupId': 'OG001'}]}, {'title': 'NYHA III', 'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}, {'title': 'NYHA IV', 'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '6 months', 'description': 'Number of participants class I-IV New York Heart Association (NYHA) functional classification, based on severity of symptoms and physical activity:\n\nNYHA I (better): No limitation of physical activity; NYHA II: Slight limitation of ordinary physical activity, breathlessness; NYHA III: marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in undue breathlessness, fatigue or palpitations; NYHA IV ( worse): unable to carry on any physical activity without discomfort.Symptoms at rest can be present. If any physical activity is undertaken discomfort is increased.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Quality of Life: MLWHFQ', 'denoms': [{'units': 'Participants', 'counts': [{'value': '138', 'groupId': 'OG000'}, {'value': '136', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '-25.01', 'spread': '23.22', 'groupId': 'OG000'}, {'value': '-26.37', 'spread': '24.53', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.75', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.91', 'ciLowerLimit': '-6.63', 'ciUpperLimit': '4.81', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': 'Quality of Life, measured by Minnesota Living with Heart Failure Questionnaire. Improvement (change) from baseline to 6 months.\n\nMinnesota Living With Heart Failure Questionnaire (MLWHFQ). The content of this questionnaire was selected to be representative of the ways heart failure and treatments can affect the key physical, emotional, social and mental dimensions of quality of life of patients with heart failure. It consist of 21-items with score 0-5. Final evaluation moves from 0 (none) to 105 (very much); a lower score means better quality of life.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'European Quality of Life Scale: EuroQol- 5 Dimension Index', 'denoms': [{'units': 'Participants', 'counts': [{'value': '138', 'groupId': 'OG000'}, {'value': '136', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '0.04', 'spread': '0.28', 'groupId': 'OG000'}, {'value': '0.08', 'spread': '0.23', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.20', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.04', 'ciLowerLimit': '-0.2', 'ciUpperLimit': '0.28', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': 'European Quality of Life Scale: EuroQol- 5 Dimension index (Range: 1 full health-0 death). It measures health status self-reported by the patient. It has 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels: 1 no problem; 2 some or moderate problems; 3 extreme problems. The EuroQol Research Foundation converts this information into a single summary index, by applying a formula that attaches specific country values (called weights) to each of the levels in each dimension. The index is calculated by subtracting the mentioned weights from 1, the value for full health.\n\nWe measured the EuroQol-5D index improvement (change) from baseline to 6 months.\n\nMore information in: EQ-5D-3L-User-Guide\\_version-6.0 (1).pdf', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Patients With Admissions Due to Heart Failure (HF)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'OG000'}, {'value': '144', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.01', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-5.5', 'ciLowerLimit': '-9.7', 'ciUpperLimit': '-1.4', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '6 months', 'description': 'Number of patients with hospital admissions due to Heart Failure. From Baseline to 6 months', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Patients With Deaths', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'title': 'mortality due to cardiovascular causes', 'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}, {'title': 'mortality due to non cardiovascular causes', 'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.71', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference in percentages', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.68', 'ciLowerLimit': '-4.2', 'ciUpperLimit': '2.87', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'NON_INFERIORITY', 'statisticalComment': 'Equivalence margin of 7%', 'nonInferiorityComment': 'Equivalence margin of 5%'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '6 months', 'description': 'Number of Patients with deaths due to Cardiovascular and non cardiovascular causes', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'ACEI % Relative Dose (Mean) With Regard to Target Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '56.13', 'spread': '30.4', 'groupId': 'OG000'}, {'value': '72.61', 'spread': '29.8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '16.5', 'ciLowerLimit': '8.7', 'ciUpperLimit': '24.3', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 7%'}], 'paramType': 'MEAN', 'timeFrame': '4 Months', 'description': 'ACEI mean Relative dose is the mean dose of ACEI achieved 4 months after starting titration, relative to target dose (%) described in European guidelines', 'unitOfMeasure': 'percentage of target dose', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'ARB % Relative Dose (Mean) With Regard to Target Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '43.51', 'spread': '33.7', 'groupId': 'OG000'}, {'value': '44.48', 'spread': '33.5', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.93', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.9', 'ciLowerLimit': '-15.1', 'ciUpperLimit': '17.1', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 7%'}], 'paramType': 'MEAN', 'timeFrame': '4 months', 'description': 'ARB, angiotensin II receptor blockers, mean relative dose ( % to target dose). Target dose is described in European guidelines.\n\nMeasured at 4 months after starting titration.', 'unitOfMeasure': 'percentage of target dose', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'During the titration process several patients that at baseline did not have ARB prescription were prescribed this drug.'}, {'type': 'SECONDARY', 'title': 'MRA % Relative Dose (Mean) With Regard to Target Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '125', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'OG001', 'title': 'HF Nurse Up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 European Society of Cardiology (ESC) HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" EF≤ 40% patients. Protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support'}], 'classes': [{'categories': [{'measurements': [{'value': '70.47', 'spread': '29.8', 'groupId': 'OG000'}, {'value': '71.00', 'spread': '32.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.86', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.5', 'ciLowerLimit': '-7.1', 'ciUpperLimit': '8.2', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'NON_INFERIORITY', 'nonInferiorityComment': 'Equivalence margin of 7%'}], 'paramType': 'MEAN', 'timeFrame': '4 months', 'description': 'MRA % relative dose (mean) is the mean dose achieved 4 months after starting titration with regard to target dose (%) described in european guidelines', 'unitOfMeasure': 'percentage of target dose', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Heart Failure (HF) Nurse Up-titration', 'description': 'Intervention:The cardiologist prescribes drugs and the HF-nurse implements the up-titration, driven by protocol based on 2012 ESC HF guidelines, with cardiologist support.\n\nUp-titration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) drugs of Heart Failure "De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients'}, {'id': 'FG001', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:The cardiologist prescribes and decides dosage following a protocol based on 2012 ESC HF guidelines, with nursing clinical and educational support.\n\nUp-titration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) drugs of Heart Failure "De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients'}], 'periods': [{'title': '4 Months Evaluation', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '164'}, {'groupId': 'FG001', 'numSubjects': '156'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '144'}, {'groupId': 'FG001', 'numSubjects': '145'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}, {'groupId': 'FG001', 'numSubjects': '11'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Working or living abroad', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'reasons not due to titration', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'HF Unit not active in summer', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': '6 Months Evaluation', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '144'}, {'groupId': 'FG001', 'numSubjects': '145'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '136'}, {'groupId': 'FG001', 'numSubjects': '138'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '7'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Working or living abroad', 'reasons': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'reasons not due to titration', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Heart Failure (HF) Cardiologist Up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.\n\nHF cardiologist up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" Left Ventricular Ejection Fraction≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines\n\nHF cardiologist up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines'}, {'id': 'BG001', 'title': 'HF Nurse Up-titration', 'description': 'Patients, following a protocol based on 2012 ESC HF guidelines. Cardiologist prescription and support\n\nHF nurse up-titration: Up-titration of Beta-Blocker (BB) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin Converting Enzyme Inhibitor (ACEI) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients, following a protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Angiotensin II Receptor Blocker (ARB) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients. Protocol based on 2012 ESC HF guidelines.\n\nHF nurse up-titration: Up-titration of Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure " De Novo" Left Ventricular Ejection Fraction ≤ 40% Patients, . Protocol based on 2012 ESC HF guidelines.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '60.64', 'spread': '12.25', 'groupId': 'BG000'}, {'value': '61.88', 'spread': '12.14', 'groupId': 'BG001'}, {'value': '61.28', 'spread': '12.19', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '38', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '83', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '118', 'groupId': 'BG000'}, {'value': '119', 'groupId': 'BG001'}, {'value': '237', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Spain', 'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'betablocker mean relative dose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '145', 'groupId': 'BG000'}, {'value': '144', 'groupId': 'BG001'}, {'value': '289', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '34.80', 'spread': '20.6', 'groupId': 'BG000'}, {'value': '34.81', 'spread': '18.16', 'groupId': 'BG001'}, {'value': '34.80', 'spread': '19.38', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'betablocker mean relative dose ( % to target dose) at baseline', 'unitOfMeasure': '% to target dose', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'n considered for baseline doses In both groups: patients, who were at the time of measuring the achieved doses after titration, the 4th month. We evaluated the 4 month titration process made by HF cardiologist vs HF nurse. Patients who left the study did not receive this intervention.'}, {'title': 'left ventricular ejection fraction %', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '27.45', 'spread': '7.25', 'groupId': 'BG000'}, {'value': '27.95', 'spread': '6.69', 'groupId': 'BG001'}, {'value': '27.71', 'spread': '6.97', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts.', 'unitOfMeasure': '%of blood leaving the heart /beat', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Nt-proBNP', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '139', 'groupId': 'BG000'}, {'value': '145', 'groupId': 'BG001'}, {'value': '284', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '3001', 'spread': '4041', 'groupId': 'BG000'}, {'value': '3425', 'spread': '5256', 'groupId': 'BG001'}, {'value': '3217', 'spread': '4697', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Nt-proBNP (N-terminal pro-B type natriuretic peptide) at discharge mean (SD)', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'other patients had BNP'}, {'title': '6 minute walking test', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '370', 'spread': '108', 'groupId': 'BG000'}, {'value': '361', 'spread': '102', 'groupId': 'BG001'}, {'value': '366', 'spread': '105', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': '6 minute walking test, meters. Six minute walking test. Measurement of exercise capacity . It provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. The six-minute walk test (6MWT) measures the distance (meters) an individual is able to walk over a total of six minutes on a hard, flat surface.', 'unitOfMeasure': 'meters', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Number of participants with New York Heart Association (NYHA) I,II,III,IV', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'title': 'NYHA I', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'NYHA II', 'measurements': [{'value': '128', 'groupId': 'BG000'}, {'value': '139', 'groupId': 'BG001'}, {'value': '267', 'groupId': 'BG002'}]}, {'title': 'NYHA III', 'measurements': [{'value': '28', 'groupId': 'BG000'}, {'value': '25', 'groupId': 'BG001'}, {'value': '53', 'groupId': 'BG002'}]}, {'title': 'NYHA IV', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Number of participants class I-IV New York Heart Association (NYHA) functional classification based on severity of symptoms and physical activity:\n\nNYHA I (better): No limitation of physical activity NYHA II: Slight limitation of ordinary physical activity, breathlessness NYHA III: marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in undue breathlessness, fatigue or palpitations NYHA IV ( worse): unable to carry on any physical activity without discomfort.Symptoms at rest can be present. If any physical activity, discomfort is increased.', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Minnesota living with heart failure questionnaire', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '45.71', 'spread': '22.21', 'groupId': 'BG000'}, {'value': '50.8', 'spread': '22.61', 'groupId': 'BG001'}, {'value': '48.31', 'spread': '22.52', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Quality of Life measured by Minnesota Living With Heart Failure Questionnaire (MLWHFQ). The content of this questionnaire was selected to be representative of the ways heart failure and treatments can affect the key physical, emotional, social and mental dimensions of quality of life of patients with heart failure. It consist of 21-items with score 0-5. Final evaluation moves from 0 (none) to 105 (very much); a lower score means better quality of life.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'European Quality of Life Scale: EuroQol- 5 Dimension index', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '156', 'groupId': 'BG000'}, {'value': '164', 'groupId': 'BG001'}, {'value': '320', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0.75', 'spread': '0.24', 'groupId': 'BG000'}, {'value': '0.73', 'spread': '0.23', 'groupId': 'BG001'}, {'value': '0.74', 'spread': '0.23', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'European Quality of Life Scale: EuroQol- 5 Dimension index (Range: 1 full health-0 death). It measures health status self-reported by the patient. It has 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels: 1 no problem; 2 moderate problems; 3 extreme problems. This information is converted into a single summary index, by applying a formula that attaches specific country values to each of the levels in each dimension, that are subtracted from 1 (the full health). EQ-5D-3L-User-Guide\\_version-6.0 (1).pdf', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'ACEI mean relative dose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '121', 'groupId': 'BG000'}, {'value': '118', 'groupId': 'BG001'}, {'value': '239', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '40.13', 'spread': '25.38', 'groupId': 'BG000'}, {'value': '45.92', 'spread': '30.06', 'groupId': 'BG001'}, {'value': '43.04', 'spread': '27.81', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'angiotensin-converting enzyme inhibitors mean relative dose ( % to target dose described in european heart failure guidelines)', 'unitOfMeasure': '% to target dose', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'n considered to calculate the mean baseline doses of ACEI in both groups: only the patients who received a prescription at baseline were included in the analysis.\n\nEvery patient was prescribed betablocker but not ACEI. Alternatively It was possible to be prescribed ARB/sacubitril-valsartan or nothing'}, {'title': 'Angiotensin II Receptor Blockers (ARB) mean relative dose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '43.20', 'spread': '20.63', 'groupId': 'BG000'}, {'value': '29.15', 'spread': '14.99', 'groupId': 'BG001'}, {'value': '33.84', 'spread': '17.95', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'ARB, angiotensin II receptor blockers, mean relative dose ( % to target dose).Target dose is described in European guidelines. Measured at baseline.', 'unitOfMeasure': '% to target dose', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'n considered to calculate the mean baseline doses of ARA in both groups: only the patients who received a prescription at baseline were included in the analysis.\n\nEvery patient was prescribed betablocker but not ARB. Alternatively It was possible to be prescribed ACEI/sacubitril-valsartan or nothing'}, {'title': 'MRA mean relative dose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'BG000'}, {'value': '125', 'groupId': 'BG001'}, {'value': '252', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '63.18', 'spread': '33.00', 'groupId': 'BG000'}, {'value': '61.4', 'spread': '33.52', 'groupId': 'BG001'}, {'value': '62.30', 'spread': '33.21', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'mineralocorticoid-receptor antagonists mean relative dose (% to target dose described in european heart failure guidelines)', 'unitOfMeasure': '% to target dose', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'n for MRA baseline doses in both groups: patients, who were at the time of measuring the achieved doses after titration, the 4th month and had a prescription during the titration period at any time.\n\nEvery patient was prescribed betablocker but not MRA. It was possible not having the need of its prescription.'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-03-01', 'size': 1819041, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-10-16T23:45', 'hasProtocol': True}, {'date': '2015-03-01', 'size': 147324, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-10-16T23:46', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'HEALTH_SERVICES_RESEARCH', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 320}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-11', 'completionDateStruct': {'date': '2019-04-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-11-26', 'studyFirstSubmitDate': '2015-05-18', 'resultsFirstSubmitDate': '2020-09-15', 'studyFirstSubmitQcDate': '2015-09-09', 'lastUpdatePostDateStruct': {'date': '2020-12-16', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-11-25', 'studyFirstPostDateStruct': {'date': '2015-09-11', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-11-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'BB % Relative Dose (Mean) With Regard to Target Dose', 'timeFrame': '4 months', 'description': 'BB mean Relative dose is the mean dose of betablockers achieved 4 months after starting titration, relative to target dose ( %) , which is the target dose of european heart failure guidelines for BB.'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With Worsening Renal Function (From Baseline to 4th Month)', 'timeFrame': '4 months', 'description': 'Number of participants with worsening renal function during the titration process (from baseline to 4 month) that could be associated to the titration process (Creatinine increase \\>50% baseline creatinine or creatinine\\>3mg/dl, or Estimated Glomerular Filtration\\<25 ml/min/1.73 m2)'}, {'measure': 'Number of Participants With Potassium (K) ≥5.5 Meq/l (From Baseline to 4 Month)', 'timeFrame': '4 months', 'description': 'Number of participants with Potassium≥ 5.5 meq/l during the titration process (from baseline to 4 month) that could be associated to this titration process'}, {'measure': 'Number of Participants With Symptomatic Hypotension (From Baseline to 4 Month)', 'timeFrame': '4 months', 'description': 'Description: Number of participants with symptomatic hypotension during the titration process (from baseline to 4 month) that could be associated to this titration process. Symptomatic hypotension defined as symptoms such as dizziness or light headedness, associated to hypotension'}, {'measure': 'Number of Participants With Heart Rate (HR) < 50 Beats Per Minute (From Baseline to 4 Month)', 'timeFrame': '4 months', 'description': 'Number of participants with Heart Rate (HR) \\< 50 beats per minute during the titration process (from baseline to 4 month) , which could be associated to the titration process. (with or without symptoms)'}, {'measure': 'Number of Patients With Atrio Ventricular (AV) Block Due to Titration', 'timeFrame': '4 months', 'description': 'Number of patients with AV Block during the titration process, associated to the BB titration'}, {'measure': 'Number of Patients With Worsening of Heart Failure Signs and Symptoms', 'timeFrame': '4 months', 'description': 'Number of patients with worsening of heart failure signs and symptoms during the titration process ( from baseline to 4 month) which could be associated to the titration process.'}, {'measure': 'Number of Patients With Admissions Due to Titration', 'timeFrame': '4 months', 'description': 'Number of patients with admissions due to titration ( not due to other causes)'}, {'measure': 'Number of Patients: Mortality Due to Titration', 'timeFrame': '4 months', 'description': 'Number of patients: Mortality due to titration ( not due to other causes)'}, {'measure': 'Number of Paticipants With Drug Stop (Some Titration Drug Withdrawal Due to Intolerance, no Need or Change to Other Treatment)', 'timeFrame': '4 months', 'description': 'number of paticipants with drug Stop ( withdrawal) that occur during the titration process that could be due to an adverse event. ( it can be not only due to an adverse event but because there is no need of this drug or its substitution for another kind of drug)'}, {'measure': 'Change in % Left Ventricular Ejection Fraction', 'timeFrame': '6 months', 'description': 'Change in % Left Ventricular Ejection Fraction (difference of change from baseline to 6 months between groups) Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts.'}, {'measure': 'N-terminal Pro-B Type Natriuretic Peptide Improvement (Nt-proBNP)', 'timeFrame': '6 months', 'description': 'Nt-proBNP (N-terminal pro-B type natriuretic peptide) Improvement (Decrease) difference of change from baseline to 6 months between groups, mean (SD)'}, {'measure': '6 Minute Walking Test', 'timeFrame': '6 months', 'description': '6 minute walking test improvement ( change) meters.Improvement (difference of change from baseline to 6 months between groups Six minute walking test. Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. It provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. The six-minute walk test (6MWT) measures the distance (meters) an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway.'}, {'measure': 'Number of Participants n(%) in New York Heart Association Functional Classification I,II,III,IV', 'timeFrame': '6 months', 'description': 'Number of participants class I-IV New York Heart Association (NYHA) functional classification, based on severity of symptoms and physical activity:\n\nNYHA I (better): No limitation of physical activity; NYHA II: Slight limitation of ordinary physical activity, breathlessness; NYHA III: marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in undue breathlessness, fatigue or palpitations; NYHA IV ( worse): unable to carry on any physical activity without discomfort.Symptoms at rest can be present. If any physical activity is undertaken discomfort is increased.'}, {'measure': 'Quality of Life: MLWHFQ', 'timeFrame': '6 months', 'description': 'Quality of Life, measured by Minnesota Living with Heart Failure Questionnaire. Improvement (change) from baseline to 6 months.\n\nMinnesota Living With Heart Failure Questionnaire (MLWHFQ). The content of this questionnaire was selected to be representative of the ways heart failure and treatments can affect the key physical, emotional, social and mental dimensions of quality of life of patients with heart failure. It consist of 21-items with score 0-5. Final evaluation moves from 0 (none) to 105 (very much); a lower score means better quality of life.'}, {'measure': 'European Quality of Life Scale: EuroQol- 5 Dimension Index', 'timeFrame': '6 months', 'description': 'European Quality of Life Scale: EuroQol- 5 Dimension index (Range: 1 full health-0 death). It measures health status self-reported by the patient. It has 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels: 1 no problem; 2 some or moderate problems; 3 extreme problems. The EuroQol Research Foundation converts this information into a single summary index, by applying a formula that attaches specific country values (called weights) to each of the levels in each dimension. The index is calculated by subtracting the mentioned weights from 1, the value for full health.\n\nWe measured the EuroQol-5D index improvement (change) from baseline to 6 months.\n\nMore information in: EQ-5D-3L-User-Guide\\_version-6.0 (1).pdf'}, {'measure': 'Number of Patients With Admissions Due to Heart Failure (HF)', 'timeFrame': '6 months', 'description': 'Number of patients with hospital admissions due to Heart Failure. From Baseline to 6 months'}, {'measure': 'Number of Patients With Deaths', 'timeFrame': '6 months', 'description': 'Number of Patients with deaths due to Cardiovascular and non cardiovascular causes'}, {'measure': 'ACEI % Relative Dose (Mean) With Regard to Target Dose', 'timeFrame': '4 Months', 'description': 'ACEI mean Relative dose is the mean dose of ACEI achieved 4 months after starting titration, relative to target dose (%) described in European guidelines'}, {'measure': 'ARB % Relative Dose (Mean) With Regard to Target Dose', 'timeFrame': '4 months', 'description': 'ARB, angiotensin II receptor blockers, mean relative dose ( % to target dose). Target dose is described in European guidelines.\n\nMeasured at 4 months after starting titration.'}, {'measure': 'MRA % Relative Dose (Mean) With Regard to Target Dose', 'timeFrame': '4 months', 'description': 'MRA % relative dose (mean) is the mean dose achieved 4 months after starting titration with regard to target dose (%) described in european guidelines'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Up-titration', 'Nursing or Nurse', 'Heart Failure'], 'conditions': ['Heart Failure']}, 'referencesModule': {'references': [{'pmid': '29154427', 'type': 'BACKGROUND', 'citation': 'Oyanguren J, Garcia-Garrido L, Nebot Margalef M, Lekuona I, Comin-Colet J, Manito N, Roure J, Ruiz Rodriguez P, Enjuanes C, Latorre P, Torcal Laguna J, Garcia-Gutierrez S; ETIFIC7 research group. Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol. ESC Heart Fail. 2017 Nov;4(4):507-519. doi: 10.1002/ehf2.12152. Epub 2017 Apr 3.'}, {'pmid': '32591295', 'type': 'RESULT', 'citation': 'Oyanguren J, Garcia-Garrido L, Nebot-Margalef M, Latorre-Garcia P, Torcal-Laguna J, Comin-Colet J, Roure J, Gonzalez-Costello J, Manito N, Garcia-Pinilla JM, Sanchez-Paule Y, Varela-Roman A, Moure M, Segovia-Cubero J, Soria T, Arana-Arri E, Lekuona I; Steering Committee on behalf of the ETIFIC research team group. Noninferiority of heart failure nurse titration versus heart failure cardiologist titration. ETIFIC multicenter randomized trial. Rev Esp Cardiol (Engl Ed). 2021 Jun;74(6):533-543. doi: 10.1016/j.rec.2020.04.016. Epub 2020 Jun 24. English, Spanish.'}, {'pmid': '34903479', 'type': 'DERIVED', 'citation': 'Oyanguren J, Diaz-Molina B, Lekuona I, Gonzalez-Costello J, Lopez-Fernandez S, Garcia-Pinilla JM, Garcia-Garrido L, Lopez-Moyano G, Manito N, Cobo-Marcos M, Nebot-Margalef M, Latorre-Garcia P, Arana-Arri E, Perez-Fernandez S, Torcal-Laguna J; ETIFIC research team group. Gender differences in drug titration among heart failure patients with reduced ejection fraction in the ETIFIC trial. Rev Esp Cardiol (Engl Ed). 2022 Aug;75(8):636-648. doi: 10.1016/j.rec.2021.11.002. Epub 2021 Dec 10. English, Spanish.'}]}, 'descriptionModule': {'briefSummary': 'Introduction: Heart Failure (HF) generates multiple hospital admissions and mortality, which are reduced with the administration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) drugs (Level of Evidence A). The effect is dose-dependent. Nevertheless, dosages are suboptimal. European Guidelines 2012 recommend close monitoring and up-titration of drugs by HF nurses. Trials are needed to evaluate their effectiveness and safety. Objective: To compare doses achieved by patients of BB, ACEI, ARB II and MRA in 4 months ( % relative to target doses) in the intervention group (HF nurse) and in the control group ( cardiologist), adverse events, Left Ventricular Ejection Fraction (LVEF), New York Heart Association (NYHA), 6 min. walking test, quality of life, Nt-proBNP, readmissions and mortality. Hypothesis: Non-inferiority. Design: Multicenter randomized controlled trial. New ("de novo") HF patients with LVEF ≤ 40%, NYHA II-III, without contraindications to BB of 17 Spanish hospitals will be included. Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration. In the control group doses are decided by the cardiologist clinical support and education being provided by nurses. Variables: age, sex, education, psycho-social level, Cardio Vascular Risk Factors (CVRF), NYHA, LVEF, ischemic cardiopathy., N-terminal pro B-type natriuretic peptide (Nt-proBNP), 6min. walking test, Creatinine/Glomerular Filtration Rate (GFR), Potassium (K), haemoglobin, Blood Pressure (BP), Heart Rate (HR), mg./drug, European Heart Failure Self-Care Behaviour Scale (EHFScBS), Minnesota Living with Heart Failure questionnaire (MLHFQ), European Quality of life Scale (EQ-5D). Expected Results: If our hypothesis were confirmed, evidence would be provided on the effectiveness of this healthcare management, that could be economically evaluated in future studies. A qualitative study also will be undertaken to explore barriers and facilitators to implementation', 'detailedDescription': 'No apply'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patient with "de novo" heart Failure and LVEF \\<= 40% admitted in hospital, without contraindications for BB prescription with cardiologist up-titration prescription and without having achieved BB target dose previous discharge and signing informed consent.\n\nExclusion Criteria:\n\n* Contraindications for BB.\n* Living in a nursing home.\n* Life expectancy \\< 6 months.\n* Unable to self-care or mental disease without caregiver.\n* Unable to weight\n* Without phone\n* Unable to go to clinic visit.'}, 'identificationModule': {'nctId': 'NCT02546856', 'acronym': 'ETIFIC', 'briefTitle': 'Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients', 'organization': {'class': 'OTHER_GOV', 'fullName': 'Hospital Galdakao-Usansolo'}, 'officialTitle': 'Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients', 'orgStudyIdInfo': {'id': 'PI14/01208'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Heart Failure (HF) cardiologist up-titration', 'description': 'Active Comparator:Cardiologist decides dosage with nursing clinical and educational support.', 'interventionNames': ['Other: Heart Failure (HF) cardiologist up-titration']}, {'type': 'EXPERIMENTAL', 'label': 'HF nurse up-titration', 'description': 'Intervention: The cardiologist prescribes drugs and, driven by protocol, the HF nurse implements the up-titration.', 'interventionNames': ['Other: Heart Failure (HF) nurse up-titration']}], 'interventions': [{'name': 'Heart Failure (HF) nurse up-titration', 'type': 'OTHER', 'description': 'Up-titration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure "De Novo" patients with Left Ventricular Ejection Fraction (LVEF)≤ 40%, following a protocol based on 2012 European Society of Cardiology (ESC) Heart Failure (HF) guidelines with cardiologist prescription and support.', 'armGroupLabels': ['HF nurse up-titration']}, {'name': 'Heart Failure (HF) cardiologist up-titration', 'type': 'OTHER', 'description': 'Up-titration of Beta-Blocker (BB), Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB) and Mineralocorticoid Receptor Antagonist (MRA) in Heart Failure "De Novo" patients with Left Ventricular Ejection Fraction (LVEF)≤ 40%, following a protocol based on 2012 European Society of Cardiology (ESC) Heart Failure (HF) guidelines. Drugs are prescribed and titrated by the cardiologist.', 'armGroupLabels': ['Heart Failure (HF) cardiologist up-titration']}]}, 'contactsLocationsModule': {'locations': [{'zip': '48960', 'city': 'Usansolo', 'state': 'Bizkaia', 'country': 'Spain', 'facility': 'Hospital de usansolo-Galdakao', 'geoPoint': {'lat': 43.22166, 'lon': -2.81567}}], 'overallOfficials': [{'name': 'Maria Juana Oyanguren, Nurse', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Osakidetza-Servicio vasco de Salud'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hospital Galdakao-Usansolo', 'class': 'OTHER_GOV'}, 'collaborators': [{'name': 'Carlos III Health Institute', 'class': 'OTHER_GOV'}, {'name': 'Basque Health Service', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Heart Failure Nurse', 'investigatorFullName': 'Maria Juana Oyanguren Artola', 'investigatorAffiliation': 'Hospital Galdakao-Usansolo'}}}}