Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
Condition: Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction
MeSH terms: Hypertension, Pulmonary; Hypertension; Heart Failure
Intervention: Ambrisentan; Placebo
Intervention description: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).; Sugar pill
Intervention MeSH terms: Ambrisentan
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Pulmonary Hypertension; Diastolic Heart Failure

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.
    

Eligibility 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