Trial Outcomes & Findings for Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy (NCT NCT00879060)
NCT ID: NCT00879060
Last Updated: 2021-04-27
Results Overview
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.
COMPLETED
PHASE4
53 participants
The time points measured were at Baseline and at 12 Months (Follow-Up).
2021-04-27
Participant Flow
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.
Participant milestones
| Measure |
Spironolactone
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.
|
Placebo Control
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.
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
27
|
|
Overall Study
COMPLETED
|
26
|
27
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
Baseline characteristics by cohort
| Measure |
Spironolactone
n=26 Participants
spironolactone: spironolactone 50mg daily
|
Placebo
n=27 Participants
spironolactone: spironolactone 50mg daily
|
Total
n=53 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40 years
STANDARD_DEVIATION 13 • n=5 Participants
|
42 years
STANDARD_DEVIATION 13 • n=7 Participants
|
41 years
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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.
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
Baseline (PINP)
|
2.1 micrograms/L
Standard Deviation 1.0
|
2.1 micrograms/L
Standard Deviation 1.2
|
|
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
12 Months (PINP)
|
0.7 micrograms/L
Standard Deviation 12
|
0.6 micrograms/L
Standard Deviation 1.3
|
|
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
Baseline (PIIINP)
|
4.7 micrograms/L
Standard Deviation 2.0
|
4.5 micrograms/L
Standard Deviation 2.5
|
|
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
12 Months (PIIINP)
|
2.0 micrograms/L
Standard Deviation 0.80
|
1.6 micrograms/L
Standard Deviation 0.80
|
|
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
Baseline (ICTP)
|
2.2 micrograms/L
Standard Deviation 1.4
|
2.5 micrograms/L
Standard Deviation 1.4
|
|
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
12 Months (ICTP)
|
2.7 micrograms/L
Standard Deviation 1.4
|
-2.3 micrograms/L
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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.
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Measure of Functional Capacity: Peak Oxygen Consumption With Exercise
Peak VO2 (Baseline)
|
30 ml/kg/min
Standard Deviation 7
|
28 ml/kg/min
Standard Deviation 7
|
|
Measure of Functional Capacity: Peak Oxygen Consumption With Exercise
Peak VO2 (12-Month Follow-Up)
|
29 ml/kg/min
Standard Deviation 8
|
29 ml/kg/min
Standard Deviation 6
|
SECONDARY outcome
Timeframe: Time points were measured at Baseline and again at 12 months (follow-up)Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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).
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class
NYHA Class (Baseline)
|
1.6 score on a scale
Standard Deviation 0.7
|
1.5 score on a scale
Standard Deviation 0.6
|
|
Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class
NYHA Class (12-Month Follow Up)
|
1.7 score on a scale
Standard Deviation 0.8
|
1.6 score on a scale
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline
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.
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')
Diastolic Function (Baseline)
|
14 Ratio
Standard Deviation 4
|
15 Ratio
Standard Deviation 7
|
|
Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')
Diastolic Function (12-month Follow-Up)
|
13 Ratio
Standard Deviation 6
|
13 Ratio
Standard Deviation 4
|
SECONDARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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).
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)
LGE Assessment of Myocardial Fibrosis (Baseline)
|
1.1 Percentage of Total LV Mass
Standard Deviation 2.5
|
2.5 Percentage of Total LV Mass
Standard Deviation 3.3
|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)
LGE Assessment of Myocardial Fibrosis (12-Month Follow-Up)
|
1.8 Percentage of Total LV Mass
Standard Deviation 2.9
|
2.8 Percentage of Total LV Mass
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up).Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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).
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)
Maximum Left Ventricular Wall Thickness (Baseline)
|
22 millimeters
Standard Deviation 7
|
21 millimeters
Standard Deviation 6
|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)
Maximum Left Ventricular Wall Thickness (12-Month Follow-Up)
|
22 millimeters
Standard Deviation 6
|
19 millimeters
Standard Deviation 3
|
SECONDARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up)Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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).
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)
LVED Cavity Size (Baseline)
|
133 mm/m^2
Standard Deviation 26
|
145 mm/m^2
Standard Deviation 46
|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)
LVED Cavity Size (12-Month Follow-Up)
|
129 mm/m^2
Standard Deviation 29
|
146 mm/m^2
Standard Deviation 44
|
SECONDARY outcome
Timeframe: The time points measured were at Baseline and at 12 Months (Follow-Up)Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
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).
Outcome measures
| Measure |
Spironolactone
n=26 Participants
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.
Spironolactone: spironolactone 50mg daily
|
Placebo Control
n=27 Participants
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.
Placebo: placebo 25mg daily
|
|---|---|---|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)
Left Atrial Dimension (Baseline)
|
40 millimeters
Standard Deviation 6
|
41 millimeters
Standard Deviation 5
|
|
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)
Left Atrial Dimension (12-Month Follow-Up)
|
40 millimeters
Standard Deviation 5
|
40 millimeters
Standard Deviation 6
|
Adverse Events
Spironolactone
Control Group
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place