Ignite Creation Date:
2025-12-25 @ 12:13 AM
Ignite Modification Date:
2025-12-31 @ 12:16 PM
Study NCT ID:
NCT02481258
Status:
COMPLETED
Last Update Posted:
2021-01-22
First Post:
2015-06-23
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001024', 'term': 'Aortic Valve Stenosis'}, {'id': 'D003251', 'term': 'Constriction, Pathologic'}, {'id': 'D002114', 'term': 'Calcinosis'}], 'ancestors': [{'id': 'D000082862', 'term': 'Aortic Valve Disease'}, {'id': 'D006349', 'term': 'Heart Valve Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014694', 'term': 'Ventricular Outflow Obstruction'}, {'id': 'D020763', 'term': 'Pathological Conditions, Anatomical'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D002128', 'term': 'Calcium Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C515616', 'term': '5-chloro-2-(5-chlorothiophene-2-sulfonylamino)-N-(4-(morpholine-4-sulfonyl)phenyl)benzamide'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Miller.Jordan@mayo.edu', 'phone': '507-293-0813', 'title': 'Jordan D. Miller, Ph.D.', 'organization': 'Mayo Clinic'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'Adverse event data were acquired during the periods of patient enrollment (from 6 months to a maximum of 12 months of treatment duration). The total study duration was 3 years.', 'description': 'Our definitions of AE and SAE do not differ from those provided on clinicaltrials.gov. For this study, adverse events were identified through regularly scheduled follow-up phone calls by study staff.', 'eventGroups': [{'id': 'EG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)', 'otherNumAtRisk': 12, 'deathsNumAtRisk': 12, 'otherNumAffected': 9, 'seriousNumAtRisk': 12, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo', 'otherNumAtRisk': 12, 'deathsNumAtRisk': 12, 'otherNumAffected': 10, 'seriousNumAtRisk': 12, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dyspnea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dizziness/Lightheadedness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 6, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nosebleed', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Rash/Dry Skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Bradycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Tired/Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Odor in urine', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Flatulence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Chest Pain/Tightness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Lower back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Mood Changes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Ankle Edema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Fall (study unrelated)', 'notes': 'Subject tripped and fell. No sustained injuries as a result.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Runny Nose (Common Cold)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hot Flashes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Prostate Cancer (study unrelated)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cholesterol lab values out of range', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Muscle Cramps/Aches', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypoglycemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hyperglycemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Indigestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dry Mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cough (related to cold/flu)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Low Hemoglobin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Arm Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Elevated Liver Enzymes', 'notes': 'Elevated liver enzymes at 6 month follow-up with clinically-indicated testing showing hepatic inflammation. Resolved after discontinuation of study drug. Not definitive whether hepatotoxicity was due to study drug or other medications taken.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hospitalization due progression of disease', 'notes': 'Patient reported to the hospital with dyspnea and fatigue. Subsequent testing revealed that patient had progressed to severe aortic valve stenosis during the follow-up period and was deemed eligible for surgery.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 12, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 12, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Changes in Aortic Valve Calcium Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 12 months\n\nAtaciguat (HMR1766)'}, {'id': 'OG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 12 months\n\nPlacebo Comparator: Matching Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '65', 'spread': '45', 'groupId': 'OG000'}, {'value': '215', 'spread': '58', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.05', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'The statistical analysis was done using an ANCOVA analysis adjusting for the baseline aortic valve calcium levels.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Power calculations were based on a two-sample t-test. A priori calculations to detect an effect size of 0.57 units indicated that that 50 patients per arm were needed to have 80% power. The actual effect size observed in the present study was 0.86.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 mos', 'description': 'This will be done using computed tomography (CT) scanning to evaluate aortic valve calcium levels, which is considered to be a "gold standard" for evaluating valvular calcium burden. As measured in Arbitrary Units (AU).', 'unitOfMeasure': 'Arbitrary Units', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Levels of Plasma Interleukin-6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)'}, {'id': 'OG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '2.3', 'spread': '1.6', 'groupId': 'OG000'}, {'value': '-0.2', 'spread': '0.4', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and reduce levels of circulating inflammatory cytokines in patients with mild to moderate CAVS. This will be done using ELISA-based measurements of interleukin-6 and tumor necrosis factor alpha in venous blood samples. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in inflammatory cytokine levels from baseline in subjects receiving HMR1766 or placebo capsules.', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'One placebo sample was not obtained/available for analysis, thereby reducing the number of data points from 11 to 10.'}, {'type': 'SECONDARY', 'title': 'Change in Aortic Valve Function: Aortic Valve Area', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)'}, {'id': 'OG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.07', 'spread': '0.03', 'groupId': 'OG000'}, {'value': '-0.129', 'spread': '0.04', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '>0.05', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Our a priori threshold for statistical significance was p \\< 0.05.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Power calculations were based on a two-sample t-tests assuming initial recruitment of 50 subjects.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:\n\n1. aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and\n2. mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.', 'unitOfMeasure': 'change in cm^2', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Left Ventricular Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)'}, {'id': 'OG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.6', 'spread': '1.5', 'groupId': 'OG000'}, {'value': '-2.8', 'spread': '1.6', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '>0.05', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Our a priori threshold for statistical significance was p \\< 0.05.', 'groupDescription': 'The statistical analysis was done using an ANCOVA analysis adjusting for the baseline aortic valve calcium levels.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Power calculations were based on a two-sample t-test.'}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. Left ventricular systolic function (measured by echocardiographic measurement of left ventricular ejection fraction) and 2. Left ventricular diastolic function (measured using the E/A ratio derived from Doppler measurements).', 'unitOfMeasure': 'percent', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Plasma Tumor Necrosis Factor Alpha', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)'}, {'id': 'OG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '1.9', 'spread': '2.3', 'groupId': 'OG000'}, {'value': '2.8', 'spread': '1.9', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, 6 months', 'description': 'Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines.', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'One placebo sample was not obtained/available for analysis, thereby reducing the number of data points from 11 to 10.'}, {'type': 'SECONDARY', 'title': 'Change in Aortic Valve Function: Transvalvular Pressure Gradient', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)'}, {'id': 'OG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '1.8', 'spread': '0.85', 'groupId': 'OG000'}, {'value': '3.6', 'spread': '0.9', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:\n\n1. aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and\n2. mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.', 'unitOfMeasure': 'change in mm Hg', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 6 months\n\nAtaciguat (HMR1766)'}, {'id': 'FG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 6 months\n\nPlacebo Comparator: Matching Placebo'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'Patients were required to complete initial testing for valve calcium and function (in addition to other tests/screening characteristics) prior to enrollment.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 12 months\n\nAtaciguat (HMR1766)'}, {'id': 'BG001', 'title': 'Matching Placebo', 'description': 'Taken Daily for 12 months\n\nPlacebo Comparator: Matching Placebo'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '74', 'spread': '4', 'groupId': 'BG000'}, {'value': '72', 'spread': '8', 'groupId': 'BG001'}, {'value': '73', 'spread': '6', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'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': '12', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '23', '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': 'United States', 'categories': [{'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Region of enrollment was confined to patients able to travel to Mayo Clinic Rochester for a minimum of 2 visits (baseline/6mo and potentially 12mo)', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2014-01-08', 'size': 624156, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2019-06-17T16:51', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 35}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-01', 'completionDateStruct': {'date': '2019-12-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-01-04', 'studyFirstSubmitDate': '2015-06-23', 'resultsFirstSubmitDate': '2019-08-06', 'studyFirstSubmitQcDate': '2015-06-23', 'lastUpdatePostDateStruct': {'date': '2021-01-22', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-01-07', 'studyFirstPostDateStruct': {'date': '2015-06-25', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-01-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-07-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Changes in Aortic Valve Calcium Levels', 'timeFrame': 'baseline, 6 mos', 'description': 'This will be done using computed tomography (CT) scanning to evaluate aortic valve calcium levels, which is considered to be a "gold standard" for evaluating valvular calcium burden. As measured in Arbitrary Units (AU).'}], 'secondaryOutcomes': [{'measure': 'Change in Levels of Plasma Interleukin-6', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and reduce levels of circulating inflammatory cytokines in patients with mild to moderate CAVS. This will be done using ELISA-based measurements of interleukin-6 and tumor necrosis factor alpha in venous blood samples. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in inflammatory cytokine levels from baseline in subjects receiving HMR1766 or placebo capsules.'}, {'measure': 'Change in Aortic Valve Function: Aortic Valve Area', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:\n\n1. aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and\n2. mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.'}, {'measure': 'Change in Left Ventricular Function', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. Left ventricular systolic function (measured by echocardiographic measurement of left ventricular ejection fraction) and 2. Left ventricular diastolic function (measured using the E/A ratio derived from Doppler measurements).'}, {'measure': 'Change in Plasma Tumor Necrosis Factor Alpha', 'timeFrame': 'Baseline, 6 months', 'description': 'Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines.'}, {'measure': 'Change in Aortic Valve Function: Transvalvular Pressure Gradient', 'timeFrame': 'baseline, 6 mos', 'description': 'Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:\n\n1. aortic valve area over time (calculated from the continuity equation) in subjects receiving HMR1766 or placebo capsules, AVA will be evaluated by both the absolute value and following normalization for body surface area, and\n2. mean transvalvular pressure gradient over time (calculated from the blood velocity trace using the Bernoulli equation) in subjects receiving HMR1766 or placebo capsules.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Stenosis', 'Aortic Valve', 'Aorta', 'Calcified', 'Calcific', 'Calcification'], 'conditions': ['Aortic Valve Stenosis']}, 'referencesModule': {'references': [{'pmid': '39989354', 'type': 'DERIVED', 'citation': 'Zhang B, Enriquez-Sarano M, Schaff HV, Michelena HI, Roos CM, Hagler MA, Zhang H, Casaclang-Verzosa G, Huang R, Bartoo A, Ranadive S, Joyner MJ, Pislaru S, Nkomo VT, Kremers WK, Araoz PA, Singh G, Walters MA, Hawkinson J, Cunningham KY, Sung J, Dunagan B, Ye Z, Miller JD. Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy. Circulation. 2025 Apr;151(13):913-930. doi: 10.1161/CIRCULATIONAHA.123.066523. Epub 2025 Feb 24.'}], 'seeAlsoLinks': [{'url': 'https://www.mayo.edu/research/clinical-trials', 'label': 'Mayo Clinic Clinical Trials'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of the current study is to determine whether Ataciguat (HMR1766) slows progression of valve calcification in patients with moderate calcific aortic valve stenosis. Secondary and tertiary objectives are to determine whether Ataciguat slows progression of aortic valve function, reduces systemic inflammation, and prevents left ventricular dysfunction in patients with moderate calcific aortic valve stenosis.', 'detailedDescription': 'Patients with Moderate Calcific Aortic Valve Stenosis may be eligible for enrollment in this study. Participation lasts 12 months, which includes a total of 3 study visits (baseline/screening visit, 6 month follow up visit and 12 month follow up visit). During each visit, a blood sample will be taken along with other research related tests (Orthostatic Tolerance Standing Test, CT Scan, Echocardiogram, DEXA Scan). Qualifying Participants will be supplied with 6 months worth of study medication or placebo during visits 1 (baseline/screening visit) and 2 (6 month follow up visit) in which they will take at home daily with food. On visit 3 (12 month follow up visit), any remaining study medication or placebo will be returned to study staff.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '50 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria\n\n1. Age \\> 50 years\n2. Male or female sex\n3. Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2\n4. Aortic valve calcium levels greater than 300 AU from chest CT\n5. Ejection fraction \\>50%\n\nExclusion Criteria\n\n1. Orthostatic intolerance or symptomatic hypotension prior to study or during study visits\n2. Positive pregnancy test during screening visit\n3. Nitrate use or α-antagonist medication use within 24 hours\n4. Systolic blood pressure \\<110 mm Hg\n5. Mean systemic arterial pressure \\<75 mm Hg\n6. Severe mitral or aortic regurgitation\n7. Retinal or optic nerve problems\n8. Recent (≤30 days) acute coronary syndrome\n9. Oxygen saturation \\<90% on room air\n10. Congenital valve disease\n11. Hepatic dysfunction/elevated liver enzymes\n12. Prescription of drugs known to alter NO-sGC-cGMP signaling (sildenafil, nitrates, etc.)\n13. Prescription of Warfarin (Coumadin) for chronic anticoagulation\n14. Concomitant participation in other trials at Mayo Clinic or elsewhere\n15. Use of phenytoin or related compounds for any indication\n16. Chronic midazolam treatment for any indication\n17. Use of monoamine oxidase inhibitors for any indication\n18. Use of anti-diabetic drugs in the sulfonylurea family'}, 'identificationModule': {'nctId': 'NCT02481258', 'acronym': 'CAVS', 'briefTitle': 'A Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification', 'organization': {'class': 'OTHER', 'fullName': 'Mayo Clinic'}, 'officialTitle': 'A Phase II Randomized, Placebo-Controlled, Double-Blinded Study Evaluating the Effects of Ataciguat (HMR1766) on Aortic Valve Calcification in Patients With Moderate Calcific Aortic Valve Stenosis', 'orgStudyIdInfo': {'id': '14-006469'}, 'secondaryIdInfos': [{'id': 'TR 000954', 'type': 'OTHER', 'domain': 'National Center for Advancing Translational Sciences'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ataciguat (HMR1766)', 'description': '200mg taken daily for 12 months', 'interventionNames': ['Drug: Ataciguat (HMR1766)']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Matching Placebo', 'description': 'Taken Daily for 12 months', 'interventionNames': ['Other: Placebo Comparator: Matching Placebo']}], 'interventions': [{'name': 'Ataciguat (HMR1766)', 'type': 'DRUG', 'armGroupLabels': ['Ataciguat (HMR1766)']}, {'name': 'Placebo Comparator: Matching Placebo', 'type': 'OTHER', 'armGroupLabels': ['Matching Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '55905', 'city': 'Rochester', 'state': 'Minnesota', 'country': 'United States', 'facility': 'Mayo Clinic in Rochester', 'geoPoint': {'lat': 44.02163, 'lon': -92.4699}}], 'overallOfficials': [{'name': 'Jordan D Miller, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Mayo Clinic'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mayo Clinic', 'class': 'OTHER'}, 'collaborators': [{'name': 'Sanofi', 'class': 'INDUSTRY'}, {'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'SAC II', 'investigatorFullName': 'Jordan D. Miller, Ph.D.', 'investigatorAffiliation': 'Mayo Clinic'}}}}