Ignite Creation Date:
2025-12-25 @ 2:11 AM
Ignite Modification Date:
2025-12-27 @ 11:18 PM
Study NCT ID:
NCT00879060
Status:
COMPLETED
Last Update Posted:
2021-04-27
First Post:
2009-04-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002312', 'term': 'Cardiomyopathy, Hypertrophic'}, {'id': 'D005355', 'term': 'Fibrosis'}], 'ancestors': [{'id': 'D009202', 'term': 'Cardiomyopathies'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D001020', 'term': 'Aortic Stenosis, Subvalvular'}, {'id': 'D001024', 'term': 'Aortic Valve Stenosis'}, {'id': 'D000082862', 'term': 'Aortic Valve Disease'}, {'id': 'D006349', 'term': 'Heart Valve Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D013148', 'term': 'Spironolactone'}], 'ancestors': [{'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'mmaron@tuftsmedicalcenter.org', 'phone': '(617) 636-8066', 'title': 'Martin Maron, MD', 'organization': 'Tufts Medical Center'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'Study population was small in size; duration of drug administration of 1 year too abbreviated to identify clinical/ structural changes in HCM; 50% patients asymptomatic (peak VO2 normal) limit opportunity for improvement with drug intervention'}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 0, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Control Group', 'description': 'A control population of age and gender-matched volunteers recruited from the general medicine outpatient clinic at Tufts Medical Center as well as from Tufts Medical Center employees. Controls will be excluded if any history of heart disease or any risk factors for cardiovascular disease, conditions of physiological or pathological activation of collagen turnover. Control subjects will have a one time blood draw of 16mL (3 teaspoons).', 'otherNumAtRisk': 27, 'deathsNumAtRisk': 27, 'otherNumAffected': 0, 'seriousNumAtRisk': 27, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '1'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily.\n\nSpironolactone: spironolactone 50mg daily'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to placebo group will be initiated on 25mg of placebo.\n\nPlacebo: placebo 25mg daily'}], 'classes': [{'title': 'Baseline (PINP)', 'categories': [{'measurements': [{'value': '2.1', 'spread': '1.0', 'groupId': 'OG000'}, {'value': '2.1', 'spread': '1.2', 'groupId': 'OG001'}]}]}, {'title': '12 Months (PINP)', 'categories': [{'measurements': [{'value': '0.7', 'spread': '12', 'groupId': 'OG000'}, {'value': '0.6', 'spread': '1.3', 'groupId': 'OG001'}]}]}, {'title': 'Baseline (PIIINP)', 'categories': [{'measurements': [{'value': '4.7', 'spread': '2.0', 'groupId': 'OG000'}, {'value': '4.5', 'spread': '2.5', 'groupId': 'OG001'}]}]}, {'title': '12 Months (PIIINP)', 'categories': [{'measurements': [{'value': '2.0', 'spread': '0.80', 'groupId': 'OG000'}, {'value': '1.6', 'spread': '0.80', 'groupId': 'OG001'}]}]}, {'title': 'Baseline (ICTP)', 'categories': [{'measurements': [{'value': '2.2', 'spread': '1.4', 'groupId': 'OG000'}, {'value': '2.5', 'spread': '1.4', 'groupId': 'OG001'}]}]}, {'title': '12 Months (ICTP)', 'categories': [{'measurements': [{'value': '2.7', 'spread': '1.4', 'groupId': 'OG000'}, {'value': '-2.3', 'spread': '1.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.0', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare continuous variable PINP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups at baseline.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}, {'pValue': '0.8', 'groupIds': ['OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.2', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare continuous variable PIIINP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups at baseline.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}, {'pValue': '0.3', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.3', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.aseline.', 'groupDescription': 'A two-sample T-test was used to compare continuous variable ICTP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups at baseline.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}, {'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.0', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable PINP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': 'Specific variables of collagen turnover markers that will be evaluated include markers of collagen synthesis (PINP, PIIINP), and marker of collagen degradation (ICTP). A two-sample t-test was used to compare the differences between these collagen turnover markers at baseline and the absolute differences in change from baseline to 12 months of follow-up.', 'unitOfMeasure': 'micrograms/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}, {'type': 'SECONDARY', 'title': 'Measure of Functional Capacity: Peak Oxygen Consumption With Exercise', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily.\n\nSpironolactone: spironolactone 50mg daily'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to placebo group will be initiated on an inactive placebo pill.\n\nPlacebo: inactive placebo pill daily'}], 'classes': [{'title': 'Peak VO2 (Baseline)', 'categories': [{'measurements': [{'value': '30', 'spread': '7', 'groupId': 'OG000'}, {'value': '28', 'spread': '7', 'groupId': 'OG001'}]}]}, {'title': 'Peak VO2 (12-Month Follow-Up)', 'categories': [{'measurements': [{'value': '29', 'spread': '8', 'groupId': 'OG000'}, {'value': '29', 'spread': '6', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.7', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '1.2', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable peak oxygen consumption with exercise (peak VO2) between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': "This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to determine if spironolactone improves a subject's functional capacity during exercise (peak oxygen consumption levels/peak VO2). Peak VO2 levels were measured in ml/kg/min.", 'unitOfMeasure': 'ml/kg/min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}, {'type': 'SECONDARY', 'title': 'Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'classes': [{'title': 'NYHA Class (Baseline)', 'categories': [{'measurements': [{'value': '1.6', 'spread': '0.7', 'groupId': 'OG000'}, {'value': '1.5', 'spread': '0.6', 'groupId': 'OG001'}]}]}, {'title': 'NYHA Class (12-Month Follow Up)', 'categories': [{'measurements': [{'value': '1.7', 'spread': '0.8', 'groupId': 'OG000'}, {'value': '1.6', 'spread': '0.7', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.8', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.0', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable New York Heart Association (NYHA) Functional Class between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Time points were measured at Baseline and again at 12 months (follow-up)', 'description': 'This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to assess heart failure symptoms according to the New York Heart Association (NYHA) functional class, which is an estimate of a patients functional ability. The NYHA functional classes include: Class I (no limitation of physical activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity), and Class IV (unable to carry out any physical acitivity without discomfort).', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}, {'type': 'SECONDARY', 'title': "Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')", 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'classes': [{'title': 'Diastolic Function (Baseline)', 'categories': [{'measurements': [{'value': '14', 'spread': '4', 'groupId': 'OG000'}, {'value': '15', 'spread': '7', 'groupId': 'OG001'}]}]}, {'title': 'Diastolic Function (12-month Follow-Up)', 'categories': [{'measurements': [{'value': '13', 'spread': '6', 'groupId': 'OG000'}, {'value': '13', 'spread': '4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '1.4', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': "A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable Septal E/e' between spironolactone treated and placebo groups.", 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': "This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to measure indices of diastolic function by Tissue Doppler Echocardiography using the Septal E/e' ratio.", 'unitOfMeasure': 'Ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline'}, {'type': 'SECONDARY', 'title': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'classes': [{'title': 'LGE Assessment of Myocardial Fibrosis (Baseline)', 'categories': [{'measurements': [{'value': '1.1', 'spread': '2.5', 'groupId': 'OG000'}, {'value': '2.5', 'spread': '3.3', 'groupId': 'OG001'}]}]}, {'title': 'LGE Assessment of Myocardial Fibrosis (12-Month Follow-Up)', 'categories': [{'measurements': [{'value': '1.8', 'spread': '2.9', 'groupId': 'OG000'}, {'value': '2.8', 'spread': '4.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.7', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.2', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable percentage of left ventricular mass (%LV) between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\\^2), and left atrial dimension (in mm).', 'unitOfMeasure': 'Percentage of Total LV Mass', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}, {'type': 'SECONDARY', 'title': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'classes': [{'title': 'Maximum Left Ventricular Wall Thickness (Baseline)', 'categories': [{'measurements': [{'value': '22', 'spread': '7', 'groupId': 'OG000'}, {'value': '21', 'spread': '6', 'groupId': 'OG001'}]}]}, {'title': 'Maximum Left Ventricular Wall Thickness (12-Month Follow-Up)', 'categories': [{'measurements': [{'value': '22', 'spread': '6', 'groupId': 'OG000'}, {'value': '19', 'spread': '3', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.4', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.9', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable maximum left ventricular wall thickness (Max LV) between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\\^2), and left atrial dimension (in mm).', 'unitOfMeasure': 'millimeters', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}, {'type': 'SECONDARY', 'title': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'classes': [{'title': 'LVED Cavity Size (Baseline)', 'categories': [{'measurements': [{'value': '133', 'spread': '26', 'groupId': 'OG000'}, {'value': '145', 'spread': '46', 'groupId': 'OG001'}]}]}, {'title': 'LVED Cavity Size (12-Month Follow-Up)', 'categories': [{'measurements': [{'value': '129', 'spread': '29', 'groupId': 'OG000'}, {'value': '146', 'spread': '44', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.7', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '5.7', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable left ventricular end-diastolic (LVED) cavity size between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up)', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic (LVED) cavity size (in mm/m\\^2), and left atrial dimension (in mm).', 'unitOfMeasure': 'mm/m^2', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}, {'type': 'SECONDARY', 'title': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'OG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'classes': [{'title': 'Left Atrial Dimension (Baseline)', 'categories': [{'measurements': [{'value': '40', 'spread': '6', 'groupId': 'OG000'}, {'value': '41', 'spread': '5', 'groupId': 'OG001'}]}]}, {'title': 'Left Atrial Dimension (12-Month Follow-Up)', 'categories': [{'measurements': [{'value': '40', 'spread': '5', 'groupId': 'OG000'}, {'value': '40', 'spread': '6', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.8', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Absolute difference', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.1', 'pValueComment': 'An a priori threshold for statistical significance was determined at an alpha level of 0.05.', 'groupDescription': 'A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable left atrial dimension between spironolactone treated and placebo groups.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up)', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\\^2), and left atrial dimension (in mm).', 'unitOfMeasure': 'millimeters', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. Serum potassium and creatinine levels will be drawn at baseline, weeks 1,4,5 and months 3,6,9, and 12. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily for 12 months of follow-up. If a subject experiences an increase in serum potassium or creatinine above these parameters at week 4, the study drug will be decreased in half from current dosage. If on 25mg daily, subject will be instructed to decrease to 25mg every other day. Subjects who experience hyperkalemia or increased creatinine levels on 25mg every other day will have the drug discontinued.'}, {'id': 'FG001', 'title': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of placebo.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}, {'groupId': 'FG001', 'numSubjects': '27'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}, {'groupId': 'FG001', 'numSubjects': '27'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Subjects diagnosed with HCM, between the ages of 18-55 (male or female), who are not pregnant were recruited from the Tufts Medical Center Hypertrophic Cardiomyopathy Center. The last patient completed the study in August of 2012.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '53', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Spironolactone', 'description': 'spironolactone: spironolactone 50mg daily'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'spironolactone: spironolactone 50mg daily'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '40', 'spread': '13', 'groupId': 'BG000'}, {'value': '42', 'spread': '13', 'groupId': 'BG001'}, {'value': '41', 'spread': '13', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '38', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '53', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': '53 HCM patients (41 +/- 13 years old, 72% men and 28% female) were randomized 1:1 to receive either 50mg of spironolactone or a placebo pill over a 12 month follow up period.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 53}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-03', 'completionDateStruct': {'date': '2012-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-03-31', 'studyFirstSubmitDate': '2009-04-08', 'resultsFirstSubmitDate': '2019-07-22', 'studyFirstSubmitQcDate': '2009-04-08', 'lastUpdatePostDateStruct': {'date': '2021-04-27', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-03-31', 'studyFirstPostDateStruct': {'date': '2009-04-09', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-04-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2011-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': 'Specific variables of collagen turnover markers that will be evaluated include markers of collagen synthesis (PINP, PIIINP), and marker of collagen degradation (ICTP). A two-sample t-test was used to compare the differences between these collagen turnover markers at baseline and the absolute differences in change from baseline to 12 months of follow-up.'}], 'secondaryOutcomes': [{'measure': 'Measure of Functional Capacity: Peak Oxygen Consumption With Exercise', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': "This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to determine if spironolactone improves a subject's functional capacity during exercise (peak oxygen consumption levels/peak VO2). Peak VO2 levels were measured in ml/kg/min."}, {'measure': 'Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class', 'timeFrame': 'Time points were measured at Baseline and again at 12 months (follow-up)', 'description': 'This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to assess heart failure symptoms according to the New York Heart Association (NYHA) functional class, which is an estimate of a patients functional ability. The NYHA functional classes include: Class I (no limitation of physical activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity), and Class IV (unable to carry out any physical acitivity without discomfort).'}, {'measure': "Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')", 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': "This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to measure indices of diastolic function by Tissue Doppler Echocardiography using the Septal E/e' ratio."}, {'measure': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\\^2), and left atrial dimension (in mm).'}, {'measure': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up).', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\\^2), and left atrial dimension (in mm).'}, {'measure': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up)', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic (LVED) cavity size (in mm/m\\^2), and left atrial dimension (in mm).'}, {'measure': 'Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)', 'timeFrame': 'The time points measured were at Baseline and at 12 Months (Follow-Up)', 'description': 'CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\\^2), and left atrial dimension (in mm).'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Fibrosis', 'Hypertrophic cardiomyopathy', 'MRI', 'Myocardial Fibrosis', 'Spironolactone'], 'conditions': ['Myocardial Fibrosis', 'Hypertrophic Cardiomyopathy']}, 'referencesModule': {'references': [{'pmid': '24998133', 'type': 'BACKGROUND', 'citation': 'Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014 Jul 8;64(1):83-99. doi: 10.1016/j.jacc.2014.05.003.'}, {'pmid': '25092278', 'type': 'BACKGROUND', 'citation': 'Chan RH, Maron BJ, Olivotto I, Pencina MJ, Assenza GE, Haas T, Lesser JR, Gruner C, Crean AM, Rakowski H, Udelson JE, Rowin E, Lombardi M, Cecchi F, Tomberli B, Spirito P, Formisano F, Biagini E, Rapezzi C, De Cecco CN, Autore C, Cook EF, Hong SN, Gibson CM, Manning WJ, Appelbaum E, Maron MS. Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation. 2014 Aug 5;130(6):484-95. doi: 10.1161/CIRCULATIONAHA.113.007094.'}, {'pmid': '27450876', 'type': 'BACKGROUND', 'citation': 'Weng Z, Yao J, Chan RH, He J, Yang X, Zhou Y, He Y. Prognostic Value of LGE-CMR in HCM: A Meta-Analysis. JACC Cardiovasc Imaging. 2016 Dec;9(12):1392-1402. doi: 10.1016/j.jcmg.2016.02.031. Epub 2016 Jul 20.'}, {'pmid': '11171784', 'type': 'BACKGROUND', 'citation': 'Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, Roberts R, Marian AJ. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation. 2001 Feb 13;103(6):789-91. doi: 10.1161/01.cir.103.6.789.'}, {'pmid': '14993121', 'type': 'BACKGROUND', 'citation': 'Tsybouleva N, Zhang L, Chen S, Patel R, Lutucuta S, Nemoto S, DeFreitas G, Entman M, Carabello BA, Roberts R, Marian AJ. Aldosterone, through novel signaling proteins, is a fundamental molecular bridge between the genetic defect and the cardiac phenotype of hypertrophic cardiomyopathy. Circulation. 2004 Mar 16;109(10):1284-91. doi: 10.1161/01.CIR.0000121426.43044.2B. Epub 2004 Mar 1.'}, {'pmid': '12668699', 'type': 'BACKGROUND', 'citation': 'Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. doi: 10.1056/NEJMoa030207. Epub 2003 Mar 31.'}, {'pmid': '14517164', 'type': 'BACKGROUND', 'citation': 'Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation. 2003 Oct 14;108(15):1831-8. doi: 10.1161/01.CIR.0000091405.00772.6E. Epub 2003 Sep 29.'}, {'pmid': '15531767', 'type': 'BACKGROUND', 'citation': 'Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL; PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med. 2004 Nov 11;351(20):2058-68. doi: 10.1056/NEJMoa042739. Epub 2004 Nov 7.'}, {'pmid': '25006726', 'type': 'BACKGROUND', 'citation': 'Pfeffer MA, Pitt B, McKinlay SM. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014 Jul 10;371(2):181-2. doi: 10.1056/NEJMc1405715. No abstract available.'}, {'pmid': '25406305', 'type': 'BACKGROUND', 'citation': "Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Heitner JF, Lewis EF, O'Meara E, Rouleau JL, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, McKinlay SM, Pitt B. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015 Jan 6;131(1):34-42. doi: 10.1161/CIRCULATIONAHA.114.013255. Epub 2014 Nov 18."}, {'pmid': '10636256', 'type': 'BACKGROUND', 'citation': 'Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol. 2000 Jan;35(1):36-44. doi: 10.1016/s0735-1097(99)00492-1.'}, {'pmid': '11094035', 'type': 'BACKGROUND', 'citation': 'Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000 Nov 28;102(22):2700-6. doi: 10.1161/01.cir.102.22.2700.'}, {'pmid': '15313958', 'type': 'BACKGROUND', 'citation': 'Querejeta R, Lopez B, Gonzalez A, Sanchez E, Larman M, Martinez Ubago JL, Diez J. Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation. 2004 Sep 7;110(10):1263-8. doi: 10.1161/01.CIR.0000140973.60992.9A. Epub 2004 Aug 16.'}, {'pmid': '29604289', 'type': 'DERIVED', 'citation': 'Maron MS, Chan RH, Kapur NK, Jaffe IZ, McGraw AP, Kerur R, Maron BJ, Udelson JE. Effect of Spironolactone on Myocardial Fibrosis and Other Clinical Variables in Patients with Hypertrophic Cardiomyopathy. Am J Med. 2018 Jul;131(7):837-841. doi: 10.1016/j.amjmed.2018.02.025. Epub 2018 Mar 28.'}]}, 'descriptionModule': {'briefSummary': 'Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy and remains the leading cause of sudden cardiac death in young people and an important cause of heart failure symptoms and death at any age. In HCM, pathological remodeling of the left ventricle involving myocardial fibrosis is likely a major contributor to cardiac dysfunction and also a nidus for the generation of ventricular arrhythmias. Serum markers of collagen turnover have been shown to reliably reflect the magnitude of myocardial fibrosis in a variety of cardiovascular diseases. In addition, aldosterone antagonist drugs have been shown to decrease fibrous tissue formation in the myocardium in certain pathologic cardiovascular states in which aldosterone production is increased. In HCM, aldosterone production is up-regulated and has been implicated in the formation of myocardial fibrosis.\n\nTherefore, the specific aims of this proposal are to:\n\n1. assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters\n2. examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters.\n3. explore the effects of a 12-month treatment with aldosterone antagonist spironolactone on heart failure status, diastolic function, arrhythmic burden, and total LV mass and quantity of fibrosis by CMR.\n\nThe results of this proposal will offer important insights into the clinical significance of myocardial fibrosis in this primary genetic cardiomyopathy. The demonstration that spironolactone decreases fibrosis and improves clinical course would provide the rational for a larger multicenter clinical trial evaluating this novel therapy for improving clinical outcome in patients with HCM.', 'detailedDescription': 'Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in the general population. Myocardial fibrosis has become a prominent and clinically relevant pathophysiologic component of this complex genetic disease, related to the risk for both sudden death and heart failure. For example, left ventricular replacement fibrosis and scarring has been implicated in triggering life threatening ventricular tachycardia/fibrillation and most recently has become a novel risk marker for sudden death, based on in vivo demonstration of extensive late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR). Extensive LGE identifies patients who benefit from primary prevention of sudden death with the implantable cardioverter-defibrillators (ICD), or who evolve to the end-stage of this disease with systolic dysfunction and consideration for heart transplant.\n\nThe mineralocorticoid aldosterone has been shown to be a mediator of myocardial fibrosis, and blockade with spironolactone normalizes collagen content in HCM murine models. In addition, aldosterone antagonists have favorable clinical effects in patients with a variety of diseases associated with myocardial scarring such as congestive heart failure, systemic hypertension, and atherosclerotic coronary artery disease. However, it is uncertain whether spironolactone would have similar effects on the clinical and phenotypic expression of a genetic disease such as HCM. Therefore, we investigated whether mineralocorticoid receptor blockade with spironolactone would reduce measures reflecting myocardial fibrosis, producing favorable LV remodeling and ultimately leading to positive clinical effects for patients with HCM.\n\nThe general aim of this study is to explore the role of fibrosis in HCM by testing the hypothesis that: the presence of magnitude of myocardial fibrosis bears clinical relevance for patients with HCM, and that mineralocorticoid receptor blockade will reduce myocardial fibrosis and thereby alter the natural history of the disease.\n\nExperimental design: prospective, randomized, double-blind, placebo-controlled trial in a consecutive HCM population at a single clinical center (Tufts Medical Center HCM Institution).\n\nStudy procedures: HCM patients were recruited from Tufts Medical Center HCM Institution population from November 2007 to June 2009. Enrolled patients were randomized into two arms; treatment arm received 25mg at the start of study and then increased to target dose of 50mg if serum potassium was \\<5.5mmol/L and serum creatinine-baseline creatinine was \\<0.5mg/dl. This arm was then followed for 12 months. The control arm of the study received 25mg of placebo over 12 months. There was an additional control arm of age and gender-matched controls without HCM in the control arm to evaluate the serum markers of collagen turnover at baseline. These controls had a one time blood draw of 15mL (3 teaspoons) to assess serum biomarkers of interest and were not be followed for 12 months.\n\nSpecific outcome measures:\n\nPrimary Outcome: examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters.\n\nSecondary Outcomes: explore the effects of a 12-month treatment with aldosterone antagonist spironolactone on heart failure status, diastolic function, arrhythmic burden, and total LV mass and quantity of fibrosis by CMR.\n\nSecondary Outcome: assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Hypertrophic cardiomyopathy\n2. Able to swallow pills\n3. No prior septal reduction therapy\n4. Negative serum or hCG pregnancy test\n\nExclusion Criteria:\n\n1. Unable or unwilling to perform treadmill cardiopulmonary exercise test\n2. Prior surgical myectomy or alcohol septal ablation\n3. Known or suspected infiltrative or glycogen storage disease\n4. Significant coronary artery disease, defined as atherosclerotic coronary artery narrowing \\>70% of the luminal diameter by coronary angiography\n5. Severe obstructive pulmonary disease, defined as forced expiratory volume in 1 second (FEV1) \\<50% of predicted.\n6. Prior intolerance or adverse reaction to aldosterone receptor antagonist.\n7. History of hyper or hypoaldosteronism\n8. Baseline serum potassium \\>5.0 mmol/L.\n9. Calculated creatinine clearance \\<30 ml/min using Cockcroft-Gault formula.\n10. Pregnant or breast feeding\n11. Poorly controlled systemic hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, during 2 clinic visits.\n12. Known conditions associated with elevated serum concentrations of PIIINP (e.g., chronic liver disease, diabetes mellitus, tumors, pulmonary fibrosis, bone and rheumatoid diseases, extensive wounds) or PINP (e.g., alcoholic liver disease, metabolic bone disease, thyroid disorders), including recent trauma (≤2 weeks) or surgery (≤6 months)\n13. Taking drugs known to directly influence collagen metabolism including, amiodorone, ACE or angiotensin II inhibitors, aldosterone antagonists, statins, glucocorticoids and estrogens\n14. Patients with ICDs/pacemakers will be recruited in the study, but will be excluded from the CMR component.'}, 'identificationModule': {'nctId': 'NCT00879060', 'briefTitle': 'Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy', 'organization': {'class': 'OTHER', 'fullName': 'Tufts Medical Center'}, 'officialTitle': 'Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy', 'orgStudyIdInfo': {'id': 'K23HL086745-01A1', 'link': 'https://reporter.nih.gov/quickSearch/K23HL086745-01A1', 'type': 'NIH'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Spironolactone', 'description': 'Experimental group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to experimental group will be initiated on 25mg of spironolactone. If at week 4, serum potassium is \\<5.5 mmol/L and serum creatinine-baseline creatinine is \\<0.5 mg/dl, the study drug will be increased to the target dose of 50mg once daily.', 'interventionNames': ['Drug: Spironolactone']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo Control', 'description': 'Placebo group includes individuals diagnosed with HCM between the ages of 18-55 (up to 50 for men). At time of randomization subjects randomized to placebo group will be initiated on an inactive placebo pill.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Spironolactone', 'type': 'DRUG', 'otherNames': ['Aldactone'], 'description': 'spironolactone 50mg daily', 'armGroupLabels': ['Spironolactone']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'inactive placebo pill daily', 'armGroupLabels': ['Placebo Control']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02111', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Tufts Medical Center', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Martin S Maron, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Tufts Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Tufts Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}