Overview

Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan

Status:
Terminated

Trial end date:
2014-01-01

Target enrollment:
0

Participant gender:
All

Summary

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.

Phase:

Phase 4

Accepts Healthy Volunteers?

Details

Lead Sponsor:

University of Texas Southwestern Medical Center

Collaborator:

Gilead Sciences

Treatments:

Ambrisentan

Criteria

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