Heart Failure With Reactive Pulmonary Hypertension
Conditions
Brief summary
The purpose of this study is to determine whether Sildenafil 20mg taken three times a day is effective in the treatment of Heart Failure with Reactive Pulmonary Hypertension. This is a double-blind, placebo controlled trial.
Detailed description
Patients will be screened at the time of a diagnositic Right Heart Catheterization. Patients will be selected based on pressures measured during this procedure, current medications, and current symptoms. At baseline a 6 minute walk test and quality of life questionnaire will be administered. Medical records will be reviewed and results of recent testing will be recorded. Qualifying participants will be randomized to receive 90 days of either placebo or sildenafil 20 mg three times a day. Randomized patients will be followed for safety and efficacy by phone and as otherwise clinically indicated. At the end of the 90 day treatment period, patients will be evaluated via 6 minute walk, quality of life questionnaire, and other diagnostic tests as clinically indicated. Primary outcome will be change in the 6 minute walk distance. Secondary outcomes will be based on clinically available results such as change in heart pressures measured by right heart catheterization and echocardiogram. At the end of the treatment period, providers and patients will be unblinded in order to optimize further treatment. To achieve statistical significance, 64 patients will be enrolled and randomized.
Interventions
DRUGSildenafil
20 mg three times daily by mouth for 90 days
DRUGPlacebo
One capsule three times daily by mouth for 90 days
Sponsors
Maya Guglin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Known chronic heart failure appropriately treated with Angiotensin converting enzyme (ACE) inhibitors and beta blockers, unless contraindicated or poorly tolerated * indication for right heart catheterization * pulmonary artery mean pressure \>25 mmHg * pulmonary capillary wedge pressure \> 15 mmHg * pulmonary vascular resistance \> 3 Wood units
Exclusion criteria
* hypersensitivity, allergy, or intolerable side effect to sildenafil * history of primary pulmonary hypertension, connective tissue disorder, severe chronic obstructive pulmonary disorder (COPD), pulmonary embolism, or left to right shunt * co-morbidities, limited exercise intolerance: * morbid obesity (BMI \>40) * COPD with oxygen dependence * severe peripheral vascular disease with intermittent claudication * status post amputation of lower extremity at any level * severe degenerative joint disease preventing normal walking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Exercise Tolerance | Baseline and 90 days | In a controlled laboratory environment, participants will be asked to walk on a treadmill as fast as they can for 6 minutes. The test will be conducted at baseline and after 90 days of treatment. Data will be presented as the change in distance (in feet) walked in 6 minutes between baseline and treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulmonary Vascular Resistance | Baseline and 90 days | Pulmonary vascular resistance will be determined by right heart catheterization. Data will be collected at baseline and at the end of treatment (90 days) |
| Change in Right Ventricular Function | Baseline and 90 day | Right ventricular function will be measured using tricuspid annular plane systolic excursion via two dimensional apical four-chamber echocardiography. Data will be collected at baseline and after 90 days of treatment |
| Change in Cardiac Output Relative to Body Surface Area (Cardiac Index) | Baseline and 90 days | cardiac output will be calculated by multiplying stroke volume by heart rate. Cardiac index will be calculated by dividing cardiac output (Liters/minute) by body surface area (meters squared). Data will be collected at baseline and the end of treatment (90 days) |
| Change in Blood Pressure | Baseline and 90 days | through standard cuff method, participants will have blood pressure measured to determine systolic and diastolic blood pressure as well as mean arterial pressure. data will be collected at baseline and 90 days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo three times per day, orally
Placebo: One capsule TID PO for 90 days | 16 |
| Sildenafil Sildenafil 20 mg three times per day, orally
Sildenafil: 20 mg TID PO for 90 days | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 2 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Sildenafil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 14 Participants | 29 Participants |
| Region of Enrollment United States | 16 participants | 17 participants | 33 participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 1 / 17 |
| other Total, other adverse events | 0 / 16 | 0 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Change in Exercise Tolerance
In a controlled laboratory environment, participants will be asked to walk on a treadmill as fast as they can for 6 minutes. The test will be conducted at baseline and after 90 days of treatment. Data will be presented as the change in distance (in feet) walked in 6 minutes between baseline and treatment.
Time frame: Baseline and 90 days
Population: Several participants were not analyzed for several reasons including death, failure to follow-up, PI withdrawal or subject withdrawal. In the Sildenafil group, 17 participants were consented while 10 were analyzed. In the Placebo group, 16 subjects were consented and 12 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Exercise Tolerance | 228 feet | Standard Error 174 |
| Sildenafil | Change in Exercise Tolerance | 135 feet | Standard Error 22 |
p-value: 0.052t-test, 2 sided
Other Pre-specified
Change in Blood Pressure
through standard cuff method, participants will have blood pressure measured to determine systolic and diastolic blood pressure as well as mean arterial pressure. data will be collected at baseline and 90 days.
Time frame: Baseline and 90 days
Other Pre-specified
Change in Cardiac Output Relative to Body Surface Area (Cardiac Index)
cardiac output will be calculated by multiplying stroke volume by heart rate. Cardiac index will be calculated by dividing cardiac output (Liters/minute) by body surface area (meters squared). Data will be collected at baseline and the end of treatment (90 days)
Time frame: Baseline and 90 days
Other Pre-specified
Change in Pulmonary Vascular Resistance
Pulmonary vascular resistance will be determined by right heart catheterization. Data will be collected at baseline and at the end of treatment (90 days)
Time frame: Baseline and 90 days
Other Pre-specified
Change in Right Ventricular Function
Right ventricular function will be measured using tricuspid annular plane systolic excursion via two dimensional apical four-chamber echocardiography. Data will be collected at baseline and after 90 days of treatment
Time frame: Baseline and 90 day