Ignite Creation Date:
2025-12-24 @ 11:30 PM
Ignite Modification Date:
2025-12-25 @ 9:18 PM
Study NCT ID:
NCT00680056
Status:
COMPLETED
Last Update Posted:
2010-01-20
First Post:
2008-05-15
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Add-on Effects of Tiotropium Over Formoterol in Exercise Tolerance on Chronic Obstructive Pulmonary Disease Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D029424', 'term': 'Pulmonary Disease, Chronic Obstructive'}, {'id': 'D029481', 'term': 'Bronchitis, Chronic'}, {'id': 'D011656', 'term': 'Pulmonary Emphysema'}], 'ancestors': [{'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D001991', 'term': 'Bronchitis'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D001982', 'term': 'Bronchial Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068759', 'term': 'Formoterol Fumarate'}, {'id': 'D000069447', 'term': 'Tiotropium Bromide'}], 'ancestors': [{'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D012602', 'term': 'Scopolamine Derivatives'}, {'id': 'D014326', 'term': 'Tropanes'}, {'id': 'D053961', 'term': 'Azabicyclo Compounds'}, {'id': 'D001372', 'term': 'Aza Compounds'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D019086', 'term': 'Bridged Bicyclo Compounds, Heterocyclic'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'dcberton@gmail.com', 'phone': '55-11-55718384', 'title': 'Danilo Berton', 'organization': 'UNIFESP'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'description': 'Serious and/or other \\[non-serious\\] adverse events were not collected/assessed', 'eventGroups': [{'id': 'EG000', 'title': 'Formoterol Plus Placebo (Tiotropium) First', 'description': 'Formoterol + Placebo (Tiotropium) in first intervention period and Formoterol + Tiotropium in second intervention period (after washout period).', 'otherNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Formoterol Plus Tiotropium First', 'description': 'Formoterol + Tiotropium in first intervention period and Formoterol + placebo in second intervention period (after washout period).', 'otherNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percentage Change in Exercise Tolerance From Baseline at 2 Weeks', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Formoterol Plus Placebo (Tiotropium) Treatment', 'description': 'Formoterol + Placebo (Tiotropium) in either first intervention period or second intervention period.'}, {'id': 'OG001', 'title': 'Formoterol Plus Tiotropium Treatment', 'description': 'Formoterol + Tiotropium in either first intervention period or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '68', 'spread': '14', 'groupId': 'OG000'}, {'value': '124', 'spread': '27', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.038', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Net)', 'ciPctValue': '95', 'paramValue': '56', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '60', 'estimateComment': 'Mean difference= Formoterol plus Tiotropium minus Formoterol plus Placebo(Tiotropium)', 'groupDescription': 'It was calculated a total sample size of a 2x2 cross-over design as 24 for a two-sided t-test achieves 85% power to infer that the mean difference is not zero, the actual mean difference is 20, the standard deviation of the differences is 15, and the significance level is 0.05', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and after 2 weeks with each treatment', 'description': 'Percentage change from baseline in time to the limit of tolerance on a high intensity constant-speed treadmill exercise test (with a speed corresponding to 80% of that obtained during incremental test)', 'unitOfMeasure': 'Percentage change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'The specific period where the patient received a given treatment were analysed together.'}, {'type': 'SECONDARY', 'title': 'Mean Score on the Transitional Dyspnea Index (TDI)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Formoterol Plus Placebo (Tiotropium) Treatment', 'description': 'Formoterol + Placebo (Tiotropium) in either first intervention period or second intervention period.'}, {'id': 'OG001', 'title': 'Formoterol Plus Tiotropium Treatment', 'description': 'Formoterol + Tiotropium in first intervention period and Formoterol + placebo in second intervention period (after washout period).'}], 'classes': [{'categories': [{'measurements': [{'value': '2.9', 'spread': '2.5', 'groupId': 'OG000'}, {'value': '3.8', 'spread': '1.8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.054', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Net)', 'ciPctValue': '95', 'paramValue': '0.88', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '2.39', 'estimateComment': 'Mean difference=Arm 2 minus Arm 1', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'After 2 week of each treatment', 'description': 'TDI is a multidimensional clinical instrument developed to provide a comprehensive assessment of change in dyspnea after an intervention, considering three components (functional impairment, magnitude of task, and magnitude of effort). It ranges from -9 (major deterioration) to +9 (major improvement).', 'unitOfMeasure': 'score on scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Formoterol Plus Placebo (Tiotropium) First', 'description': 'Formoterol + Placebo (Tiotropium) in first intervention period and Formoterol + Tiotropium in second intervention period (after washout period).'}, {'id': 'FG001', 'title': 'Formoterol Plus Tiotropium First', 'description': 'Formoterol + Tiotropium in first intervention period and Formoterol + placebo in second intervention period (after washout period).'}], 'periods': [{'title': 'First Intervention', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '17'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Mainly Exacerbation of COPD', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}]}, {'title': 'Washout Period of One Week', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Second Intervention', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '14'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'University clinic Period: January-August (2008)', 'preAssignmentDetails': 'After screening and before first baseline visit, patients discontinued long-acting β2-agonists and inhaled anticholinergic bronchodilators (run in period).\n\n50 patients recruited; 33 screened. 7 excluded: 4 due to chronic obstructive pulmonary disease (COPD) exacerbation and 3 due to protocol violation.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '33', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Formoterol Plus Placebo (Tiotropium) First', 'description': 'Formoterol + Placebo (Tiotropium) in first intervention period and Formoterol + Tiotropium in second intervention period (after washout period).'}, {'id': 'BG001', 'title': 'Formoterol Plus Tiotropium First', 'description': 'Formoterol + Tiotropium in first intervention period and Formoterol + placebo in second intervention period (after washout period).'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0.0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '16.0', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '17.0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '62.0', 'spread': '8.2', 'groupId': 'BG000'}, {'value': '67.2', 'spread': '6.8', 'groupId': 'BG001'}, {'value': '64.9', 'spread': '8.5', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '7.0', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '26.0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Brazil', 'categories': [{'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '33.0', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 33}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2009-10', 'completionDateStruct': {'date': '2009-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2010-01-12', 'studyFirstSubmitDate': '2008-05-15', 'resultsFirstSubmitDate': '2009-01-26', 'studyFirstSubmitQcDate': '2008-05-15', 'lastUpdatePostDateStruct': {'date': '2010-01-20', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2009-10-30', 'studyFirstPostDateStruct': {'date': '2008-05-19', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2009-12-03', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2008-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage Change in Exercise Tolerance From Baseline at 2 Weeks', 'timeFrame': 'Baseline and after 2 weeks with each treatment', 'description': 'Percentage change from baseline in time to the limit of tolerance on a high intensity constant-speed treadmill exercise test (with a speed corresponding to 80% of that obtained during incremental test)'}], 'secondaryOutcomes': [{'measure': 'Mean Score on the Transitional Dyspnea Index (TDI)', 'timeFrame': 'After 2 week of each treatment', 'description': 'TDI is a multidimensional clinical instrument developed to provide a comprehensive assessment of change in dyspnea after an intervention, considering three components (functional impairment, magnitude of task, and magnitude of effort). It ranges from -9 (major deterioration) to +9 (major improvement).'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Pulmonary Disease, Chronic Obstructive', 'Tiotropium', 'Formoterol', 'Bronchodilator Agents', 'Exercise Tolerance', 'Randomized Controlled Trial [Publication Type]', 'COPD'], 'conditions': ['Pulmonary Disease, Chronic Obstructive', 'Chronic Bronchitis', 'Pulmonary Emphysema']}, 'referencesModule': {'references': [{'pmid': '20580216', 'type': 'DERIVED', 'citation': 'Berton DC, Reis M, Siqueira AC, Barroco AC, Takara LS, Bravo DM, Andreoni S, Neder JA. Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD. Respir Med. 2010 Sep;104(9):1288-96. doi: 10.1016/j.rmed.2010.05.017. Epub 2010 Jun 26.'}]}, 'descriptionModule': {'briefSummary': 'The primary objective is to comparatively evaluate the isolated effects of a long-acting beta2-adrenergic (formoterol fumarate 12µg b.i.d. via Aeroliser) and combined with a long-acting anti-cholinergic (tiotropium bromide 18µg o.d via Handihaler) on breathlessness, dynamic hyperinflation and exercise tolerance in patients with advanced, but stable, chronic obstructive pulmonary disease. The study hypothesis is that combining long acting bronchodilators with different action mechanisms would promote synergistic effects on clinical outcomes.', 'detailedDescription': 'This will be a single center, randomized, double-blind study consisting of two 2-week treatment periods separated by a 5-7 days washout phase without long-acting bronchodilators. Eligible patients who complete the one week screening phase will be randomized to one of two treatment sequences: 1) Formoterol --\\> Formoterol + Tiotropium or 2) Formoterol + Tiotropium --\\> Formoterol. During the treatment periods, patients will be allowed to use a short-acting beta2-adrenergic+short-acting anticholinergic as rescue medication (salbutamol+ipratropium via MDI)'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* COPD patients aged ≥ 40 years with stable moderate-to-severe airflow obstruction (FEV1 \\< 70% and FEV1/FVC ≤ 70% of predicted normal value) post-bronchodilator\n* presenting with a long history of smoking (\\> 20 pack-years) and chronic breathlessness (Baseline Dyspnoea Index total score \\< 9)\n\nExclusion Criteria:\n\n* significant cardiovascular disease, hospitalization for COPD exacerbation or presence of a respiratory tract infection within 1 month of screening\n* current or childhood asthma\n* a history of allergic rhinitis or other atopic disease\n* inability to interrupt usual bronchodilator medication\n* use of oral steroids within a month before screening\n* need for long-term oxygen therapy, arterial oxygen saturation \\< 85% at rest anemia, hypo- and hyperthyroidism, hyperadrenergic state\n* uncontrolled insulin dependent diabetes mellitus, malignancy, or any disease or condition which limits exercise performance other than COPD\n* change in inhaled corticosteroid or theophylline use within 1 month prior to screening'}, 'identificationModule': {'nctId': 'NCT00680056', 'briefTitle': 'Add-on Effects of Tiotropium Over Formoterol in Exercise Tolerance on Chronic Obstructive Pulmonary Disease Patients', 'organization': {'class': 'OTHER', 'fullName': 'Federal University of São Paulo'}, 'officialTitle': 'Randomised Cross-over Study to Compare the Effect of Formoterol Plus Tiotropium Versus Formoterol Monotherapy on Breathlessness, Dynamic Hyperinflation and Exercise Tolerance in Moderate-to-severe Stable COPD Patients', 'orgStudyIdInfo': {'id': 'TIOFOR'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': '1', 'description': 'Formoterol plus Placebo (Tiotropium)', 'interventionNames': ['Drug: Formoterol plus Placebo (Tiotropium)']}, {'type': 'EXPERIMENTAL', 'label': '2', 'description': 'Formoterol plus Tiotropium', 'interventionNames': ['Drug: Formoterol plus Tiotropium']}], 'interventions': [{'name': 'Formoterol plus Placebo (Tiotropium)', 'type': 'DRUG', 'description': 'Formoterol 12mcg-capsules (2x/d) + Placebo (Tiotropium) (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks.', 'armGroupLabels': ['1']}, {'name': 'Formoterol plus Tiotropium', 'type': 'DRUG', 'description': 'Formoterol 12mcg-capsule (2x/dia) + Tiotropium 18mcg-capsule (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks.', 'armGroupLabels': ['2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '04020-050', 'city': 'São Paulo', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE)', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}], 'overallOfficials': [{'name': 'J Alberto Neder, MD, phD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Federal University of São Paulo'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Federal University of São Paulo', 'class': 'OTHER'}, 'responsibleParty': {'oldNameTitle': 'J Alberto Neder', 'oldOrganization': 'Federal University of Sao Paulo'}}}}