Diastolic Heart Failure
Conditions
Brief summary
The aim of this study was to determine whether long-term (≥ 6 months at the target dose) blockade of ETA receptors using sitaxsentan showed functional benefit in subjects with chronic Heart Failure and an Left Ventricular Ejection Fraction ≥50%.
Interventions
DRUGSitexsentin sodium
sitaxsentan 100 mg (target dose) 0rally once daily. A 10-week Run-In Phase was conducted where dosing commenced at 25 mg daily for 2 weeks, and then was stepped up to 50 mg daily for 2 weeks, to 75 mg daily for 2 weeks and then to 100 mg daily for 2 weeks, with an additional 2-week stabilization period (10 weeks total) to a target study dose of 100 mg daily. During the Run-In Phase, if a subject was not able to tolerate upward dose titration to the target dose of 100 mg, the investigator may have elected to continue at the current dosage or reduce the dosage of sitaxsentan or placebo to the subject's immediate prior dose. During the Maintenance Phase, subjects received the highest titrated dose reached of study drug and continued it through the last day of Week M24 of the Maintenance Phase (14 weeks)- total study drug treatment duration= 6 months
DRUGPlacebo
placebo identical to the study drug in description, dose and duration
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 or older with chronic heart failure and evidence of diastolic dysfunction on echocardiogram, heart imaging, and a minimum exercise tolerance average time of 120 seconds on two treadmill tests within 2 weeks of enrollment
Exclusion criteria
* unstable cardiovascular disease within 4 weeks of screening, history of heart attack, cardiac by-pass surgery or percutaneous intervention, stent placement, within 3 months of screening or amyloidosis, hypertrophic obstructive or restrictive cardiomyopathy, or constrictive pericarditis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24 | Baseline, Week 24 (Maintenance Phase) | Treadmill exercise test is used to assess the functional capacity of participants with cardiac disease. Treadmill exercise test was conducted using the 2 minute incremental Naughton protocol. The Naughton protocol starts with a 2 minute warm-up. The speed of treadmill is set to 1 mile per hour (mph) and the incline is set to 0. After the warm-up, the speed is set at 2 mph for the remainder of the test. The test consists of six, 2 minute intervals. The grade starts at 0 for the first interval, and increases by 3.5 percent every 2 minutes. The change in total exercise time (in seconds) during the treadmill test was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Baseline, Week 24 (Maintenance Phase) | Left ventricular mass was used as a parameter for the assessment of cardiac function. An increase in left ventricular mass leads to ventricular hypertrophy which is a prognostic factor of cardiovascular morbidity and mortality. Left ventricular mass was measured by ECHO, which was calculated as (1.04 \* \[{left ventricular end diastolic diameter (LVEDD) + septal diastolic thickness + post wall diastolic thickness}\^3 - LVEDD\^3\]) \* 0.8 + 0.6. Left ventricular mass was assessed for the two ECHO modes: parasternal long-axis two dimensional (PLAX 2D) mode and parasternal short-axis view motion (PSAX M) mode. |
| Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24 | Baseline, Week 24 (Maintenance Phase) | The MLHF is a 21-item questionnaire which used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL total score was calculated as the sum of the 21 individual QoL questions. The MLHF QoL total score ranged from 0 to 105, where higher scores indicated worse health condition. |
| Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24 | Baseline, Week 24 (Maintenance Phase) | Ratio of E to E' is used as a predictor of first cardiac events. Ratio of E to E' was measured using imaging techniques based on Doppler principles. Transmitral inflow velocity was measured by Doppler echocardiography (ECHO) and the early diastolic velocity of the mitral annulus was measured by tissue Doppler imaging (TDI). |
| Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24 | Baseline, Week M24 (Maintenance Phase) | The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL emotional score was calculated as the sum of the 5 emotional domain QoL questions. The MLHF QoL emotional score ranged from 0 to 25, where higher scores indicated worse health condition. |
| Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Baseline, Week 24 (Maintenance Phase) | Participants were classified by NYHA functional class. NYHA class I: participants with cardiac disease but without resulting limitations of physical activity, NYHA class II: participants with cardiac disease resulting in slight limitation of physical activity, NYHA class III: participants with cardiac disease resulting in marked limitation of physical activity, NYHA class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Baseline was reported by NYHA functional class and the change from baseline in the functional class was reported as improvement (positive change from baseline), no change and deterioration (negative change from baseline). |
| Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24 | Baseline, Week 24 (Maintenance Phase) | The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL physical score was calculated as the sum of the 8 physical domain QoL questions. The MLHF QoL physical score ranged from 0 to 40, where higher scores indicated worse health condition. |
Countries
Canada, United States
Participant flow
Pre-assignment details
Study consisted of a 10-week dose adjusting Run-In Phase followed by a 24-week Maintenance Phase.
Participants by arm
| Arm | Count |
|---|---|
| Sitaxsentan During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks. | 127 |
| Placebo Participants received placebo matched to sitaxsentan orally once daily for 34 weeks (10-Week Run-In Phase and 24-Week Maintenance Phase). | 64 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Phase (24 Weeks) | Adverse Event | 2 | 1 |
| Maintenance Phase (24 Weeks) | Death | 1 | 0 |
| Maintenance Phase (24 Weeks) | Elevation in Liver Enzyme Values | 1 | 0 |
| Maintenance Phase (24 Weeks) | Other | 1 | 0 |
| Maintenance Phase (24 Weeks) | Physician Decision | 1 | 0 |
| Maintenance Phase (24 Weeks) | Required Chronic Heart Failure Treatment | 0 | 1 |
| Maintenance Phase (24 Weeks) | Sponsor Decision | 4 | 0 |
| Maintenance Phase (24 Weeks) | Treatment Interrupted More Than 7 Days | 1 | 2 |
| Maintenance Phase (24 Weeks) | Withdrawal by Subject | 3 | 4 |
| Run-In-Phase (10 Weeks) | Adverse Event | 5 | 1 |
| Run-In-Phase (10 Weeks) | Other | 4 | 1 |
| Run-In-Phase (10 Weeks) | Physician Decision | 0 | 1 |
| Run-In-Phase (10 Weeks) | Sponsor Decision | 6 | 3 |
| Run-In-Phase (10 Weeks) | Treatment Interrupted More Than 7 Days | 3 | 2 |
| Run-In-Phase (10 Weeks) | Unable to Tolerate 25 mg Dose | 1 | 0 |
| Run-In-Phase (10 Weeks) | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | Sitaxsentan | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.0 Years STANDARD_DEVIATION 10.94 | 64.7 Years STANDARD_DEVIATION 9.99 | 64.9 Years STANDARD_DEVIATION 10.61 |
| Sex: Female, Male Female | 76 Participants | 45 Participants | 121 Participants |
| Sex: Female, Male Male | 51 Participants | 19 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 107 / 127 | 54 / 64 |
| serious Total, serious adverse events | 25 / 127 | 16 / 64 |
Outcome results
Primary
Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24
Treadmill exercise test is used to assess the functional capacity of participants with cardiac disease. Treadmill exercise test was conducted using the 2 minute incremental Naughton protocol. The Naughton protocol starts with a 2 minute warm-up. The speed of treadmill is set to 1 mile per hour (mph) and the incline is set to 0. After the warm-up, the speed is set at 2 mph for the remainder of the test. The test consists of six, 2 minute intervals. The grade starts at 0 for the first interval, and increases by 3.5 percent every 2 minutes. The change in total exercise time (in seconds) during the treadmill test was reported.
Time frame: Baseline, Week 24 (Maintenance Phase)
Population: Intent-to-treat (ITT) population was defined as all participants who received at least 1 dose of study drug and had at least 1 valid treadmill test value at baseline and post-baseline during maintenance phase. Last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitaxsentan | Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24 | Baseline | 424.5 Seconds |
| Sitaxsentan | Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24 | Change at Week 24 | 89.5 Seconds |
| Placebo | Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24 | Baseline | 485.0 Seconds |
| Placebo | Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24 | Change at Week 24 | 37.0 Seconds |
Comparison: The median of the treatment difference was calculated using the Hodges-Lehmann estimator.p-value: 0.0302ANCOVA
Secondary
Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24
Left ventricular mass was used as a parameter for the assessment of cardiac function. An increase in left ventricular mass leads to ventricular hypertrophy which is a prognostic factor of cardiovascular morbidity and mortality. Left ventricular mass was measured by ECHO, which was calculated as (1.04 \* \[{left ventricular end diastolic diameter (LVEDD) + septal diastolic thickness + post wall diastolic thickness}\^3 - LVEDD\^3\]) \* 0.8 + 0.6. Left ventricular mass was assessed for the two ECHO modes: parasternal long-axis two dimensional (PLAX 2D) mode and parasternal short-axis view motion (PSAX M) mode.
Time frame: Baseline, Week 24 (Maintenance Phase)
Population: ITT population defined as all participants who received at least 1 dose of study drug and had at least 1 valid treadmill test value at baseline and post-baseline during maintenance phase. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure and 'Number Analyzed' signifies the participants who were evaluable at the specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Baseline: PLAX 2D mode | 217.73 Centimeter^3 | Standard Deviation 80.467 |
| Sitaxsentan | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Baseline: PSAX M-mod | 229.88 Centimeter^3 | Standard Deviation 70.251 |
| Sitaxsentan | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Change at Week 24: PLAX 2D mode | 3.09 Centimeter^3 | Standard Deviation 43.647 |
| Sitaxsentan | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Change at Week 24: PSAX M-mode | 5.60 Centimeter^3 | Standard Deviation 45.641 |
| Placebo | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Change at Week 24: PSAX M-mode | 4.83 Centimeter^3 | Standard Deviation 10.565 |
| Placebo | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Baseline: PLAX 2D mode | 226.14 Centimeter^3 | Standard Deviation 83.415 |
| Placebo | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Change at Week 24: PLAX 2D mode | -7.52 Centimeter^3 | Standard Deviation 42.582 |
| Placebo | Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24 | Baseline: PSAX M-mod | 229.19 Centimeter^3 | Standard Deviation 108.891 |
Comparison: Change at Week 24 for PLAX 2D modep-value: 0.3874ANCOVA
Comparison: Change at Week 24 for PSAX M-modep-value: 0.7038ANCOVA
Secondary
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24
The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL emotional score was calculated as the sum of the 5 emotional domain QoL questions. The MLHF QoL emotional score ranged from 0 to 25, where higher scores indicated worse health condition.
Time frame: Baseline, Week M24 (Maintenance Phase)
Population: ITT population. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24 | Baseline | 8.97 Units on a scale | Standard Deviation 7.562 |
| Sitaxsentan | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24 | Change at Week 24 | -1.87 Units on a scale | Standard Deviation 6.094 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24 | Baseline | 7.37 Units on a scale | Standard Deviation 6.914 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24 | Change at Week 24 | -1.40 Units on a scale | Standard Deviation 5.815 |
p-value: 0.8649ANCOVA
Secondary
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24
The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL physical score was calculated as the sum of the 8 physical domain QoL questions. The MLHF QoL physical score ranged from 0 to 40, where higher scores indicated worse health condition.
Time frame: Baseline, Week 24 (Maintenance Phase)
Population: ITT population. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24 | Baseline | 21.73 Units on a scale | Standard Deviation 11.74 |
| Sitaxsentan | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24 | Change at Week 24 | -4.06 Units on a scale | Standard Deviation 10.365 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24 | Baseline | 18.85 Units on a scale | Standard Deviation 10.151 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24 | Change at Week 24 | -2.35 Units on a scale | Standard Deviation 8.753 |
p-value: 0.7245ANCOVA
Secondary
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24
The MLHF is a 21-item questionnaire which used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL total score was calculated as the sum of the 21 individual QoL questions. The MLHF QoL total score ranged from 0 to 105, where higher scores indicated worse health condition.
Time frame: Baseline, Week 24 (Maintenance Phase)
Population: ITT population. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24 | Baseline | 43.79 Units on a scale | Standard Deviation 26.1 |
| Sitaxsentan | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24 | Change at Week 24 | -8.20 Units on a scale | Standard Deviation 21.493 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24 | Baseline | 37.67 Units on a scale | Standard Deviation 23.559 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24 | Change at Week 24 | -6.31 Units on a scale | Standard Deviation 18.909 |
p-value: 0.8998ANCOVA
Secondary
Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24
Ratio of E to E' is used as a predictor of first cardiac events. Ratio of E to E' was measured using imaging techniques based on Doppler principles. Transmitral inflow velocity was measured by Doppler echocardiography (ECHO) and the early diastolic velocity of the mitral annulus was measured by tissue Doppler imaging (TDI).
Time frame: Baseline, Week 24 (Maintenance Phase)
Population: ITT population was defined as all the participants who received at least 1 dose of study drug and had at least 1 valid treadmill test value at baseline and post-baseline during maintenance phase. Here, Overall Number of Participants Analyzed signifies number of participants who were evaluable for this outcome measure and 'Number Analyzed' signifies the participants who were evaluable at the specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan | Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24 | Baseline | 13.72 Ratio | Standard Deviation 6.975 |
| Sitaxsentan | Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24 | Change at Week 24 | -0.12 Ratio | Standard Deviation 4.404 |
| Placebo | Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24 | Baseline | 14.45 Ratio | Standard Deviation 6.565 |
| Placebo | Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24 | Change at Week 24 | 0.38 Ratio | Standard Deviation 4.498 |
p-value: 0.495ANCOVA
Secondary
Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24
Participants were classified by NYHA functional class. NYHA class I: participants with cardiac disease but without resulting limitations of physical activity, NYHA class II: participants with cardiac disease resulting in slight limitation of physical activity, NYHA class III: participants with cardiac disease resulting in marked limitation of physical activity, NYHA class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Baseline was reported by NYHA functional class and the change from baseline in the functional class was reported as improvement (positive change from baseline), no change and deterioration (negative change from baseline).
Time frame: Baseline, Week 24 (Maintenance Phase)
Population: ITT population. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sitaxsentan | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Baseline: Class III | 38 Participants |
| Sitaxsentan | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | No change | 60 Participants |
| Sitaxsentan | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Improvement | 30 Participants |
| Sitaxsentan | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Deterioration | 6 Participants |
| Sitaxsentan | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Baseline: Class II | 58 Participants |
| Placebo | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Deterioration | 0 Participants |
| Placebo | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Baseline: Class II | 27 Participants |
| Placebo | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Baseline: Class III | 25 Participants |
| Placebo | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | Improvement | 18 Participants |
| Placebo | Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24 | No change | 34 Participants |
Comparison: Change at Week 24p-value: 0.5909Cochran-Mantel-Haenszel