Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 7/11/2015 |
| Start Date: | January 2009 |
| End Date: | January 2014 |
| Contact: | Kelly M Chin, MD |
| Email: | kelly.chin@utsouthwestern.edu |
| Phone: | 214-645-6486 |
Safety and Efficacy Trial Using Ambrisentan for Pulmonary Hypertension Associated With Congestive Heart Failure With Preserved Left Ventricular Ejection Fraction
This is a randomized study of ambrisentan that will last 16 weeks. The study will include
patients with diastolic heart failure and pulmonary hypertension. Patients will be
randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be
started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated.
Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and
the required monthly laboratory tests (liver function testing and pregnancy testing, if
applicable), will be performed. Patients will also complete an exercise test (six minute
walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An
echocardiogram and a right heart catheterization and left ventricular end diastolic pressure
measurement will be performed at the 16 week visit. The primary end-point is safety, and
secondary end-points include the catheterization results, echocardiogram results, the walk
distance and the quality of life survey. The expected completion of the study is 18 months
from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
patients with diastolic heart failure and pulmonary hypertension. Patients will be
randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be
started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated.
Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and
the required monthly laboratory tests (liver function testing and pregnancy testing, if
applicable), will be performed. Patients will also complete an exercise test (six minute
walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An
echocardiogram and a right heart catheterization and left ventricular end diastolic pressure
measurement will be performed at the 16 week visit. The primary end-point is safety, and
secondary end-points include the catheterization results, echocardiogram results, the walk
distance and the quality of life survey. The expected completion of the study is 18 months
from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
Hypothesis: patients with pulmonary hypertension secondary to diastolic congestive heart
failure (CHF) treated with ambrisentan for 16 weeks will have improved hemodynamics,
increased exercise capacity and improved functional class with an acceptable safety profile,
compared with placebo treated patients.
Objectives: to evaluate the safety and efficacy of ambrisentan treatment in patients with
pulmonary hypertension due to diastolic CHF. Efficacy will be assessed by improvement in
hemodynamics (PVR(Pulmonary Vascular Resistance): primary efficacy endpoint), six minute
walk distance (6MWD), World Health Organization (WHO) functional class and quality of life
after 16 weeks of treatment with ambrisentan. Safety of ambrisentan will be compared to
placebo.
Concomitant Medication: Treatment with standard medications for CHF including diuretics and
optimal blood pressure control with antihypertensive medications will be allowed throughout
the study period. Diuretics adjustment will also be allowed and encouraged based on the
planned diuretic management protocol. Approved medications for CHF in general are allowed as
well, though it should be noted that there are no medications shown to have benefit in
diastolic CHF. Patients may not be on an endothelin antagonist or sildenafil.
failure (CHF) treated with ambrisentan for 16 weeks will have improved hemodynamics,
increased exercise capacity and improved functional class with an acceptable safety profile,
compared with placebo treated patients.
Objectives: to evaluate the safety and efficacy of ambrisentan treatment in patients with
pulmonary hypertension due to diastolic CHF. Efficacy will be assessed by improvement in
hemodynamics (PVR(Pulmonary Vascular Resistance): primary efficacy endpoint), six minute
walk distance (6MWD), World Health Organization (WHO) functional class and quality of life
after 16 weeks of treatment with ambrisentan. Safety of ambrisentan will be compared to
placebo.
Concomitant Medication: Treatment with standard medications for CHF including diuretics and
optimal blood pressure control with antihypertensive medications will be allowed throughout
the study period. Diuretics adjustment will also be allowed and encouraged based on the
planned diuretic management protocol. Approved medications for CHF in general are allowed as
well, though it should be noted that there are no medications shown to have benefit in
diastolic CHF. Patients may not be on an endothelin antagonist or sildenafil.
Inclusion Criteria:
1. Catheterization
1. Elevated pulmonary arterial pressure (PA mean >25mmHg)
2. Elevated pulmonary vascular resistance (>240 dynes.cm.sec-5) or transpulmonary
gradient (>12 mmHg)
3. Elevated LVEDP (>15mmHg, but ≤23 mmHg)
2. Evidence of left ventricular diastolic dysfunction: LA>4.0, LVH or diastolic
dysfunction by mitral filling pattern
3. Echocardiogram: Normal or mildly reduced LV ejection fraction (greater than or equal
to 40%)
4. Symptomatic chronic HF (WHO functional class II-IV)
5. Baseline walk distance 100 to 400 meters
6. Age 18 - 80 (increased from 70)
Maximal treatment of diastolic dysfunction as noted by the treating physicians with no
change in medical therapy for one month prior to entry
Exclusion Criteria:
1. Use of endothelin receptor antagonist, prostacyclin or PDE-5 inhibitor within 4 weeks
of enrollment
2. Exercise capacity limited by other illness (other lung disease, arthritis, mobility
limitations)
3. Uncontrolled systemic hypertension
4. Uncontrolled atrial fibrillation
5. Severe valvular disease
6. Pregnant females- females of child bearing potential will need to use contraceptive
agent barrier given the teratogenicity associated with ERA's
7. Uncontrolled OSA
We found this trial at
1
site
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
Click here to add this to my saved trials
