Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
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.
Heart Failure With Preserved Ejection Fraction
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
|Official Title:||Safety and Efficacy Trial Using Ambrisentan for Pulmonary Hypertension Associated With Congestive Heart Failure With Preserved Left Ventricular Ejection Fraction|
- The primary outcome will be a safety evaluation. The primary efficacy outcome will be Pulmonary Vascular Resistance. [ Time Frame: Four months ] [ Designated as safety issue: Yes ]
- The secondary endpoints will be 6 MWD, WHO functional class, and SF-36 quality of life assessment. [ Time Frame: Four months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||January 2014|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
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).
Other Name: Letairis
|Placebo Comparator: 2||
Other Name: The placebo will look identical to the Ambrisentan tablets
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00840463
|United States, Texas|
|UT Southwestern Medical Center|
|Dallas, Texas, United States, 75390-8550|
|Principal Investigator:||Kelly M Chin, MD||UT Southwestern Medical Center|
|Principal Investigator:||Fernando Torres, MD||UT Southwestern Medical Center|