Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pulmonary Hypertension Heart Failure With Preserved Ejection Fraction	Drug: Ambrisentan Other: Placebo	Phase 4


Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure Pulmonary Hypertension

Drug Information available for: Ambrisentan

U.S. FDA Resources

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]


Enrollment:	3
Study Start Date:	January 2009
Study Completion Date:	January 2014
Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1	Drug: Ambrisentan 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: Placebo Sugar pill Other Name: The placebo will look identical to the Ambrisentan tablets

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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)
Evidence of left ventricular diastolic dysfunction: LA>4.0, LVH or diastolic dysfunction by mitral filling pattern
Echocardiogram: Normal or mildly reduced LV ejection fraction (greater than or equal to 40%)
Symptomatic chronic HF (WHO functional class II-IV)
Baseline walk distance 100 to 400 meters
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:

Use of endothelin receptor antagonist, prostacyclin or PDE-5 inhibitor within 4 weeks of enrollment
Exercise capacity limited by other illness (other lung disease, arthritis, mobility limitations)
Uncontrolled systemic hypertension
Uncontrolled atrial fibrillation
Severe valvular disease
Pregnant females- females of child bearing potential will need to use contraceptive agent barrier given the teratogenicity associated with ERA's
Uncontrolled OSA

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00840463

Locations


United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390-8550

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Gilead Sciences

Investigators


Principal Investigator:	Kelly M Chin, MD	UT Southwestern Medical Center
Principal Investigator:	Fernando Torres, MD	UT Southwestern Medical Center

More Information


Responsible Party:	Kelly M Chin, Assistant Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00840463 History of Changes
Other Study ID Numbers:	IN-US-300-0126
Study First Received:	February 6, 2009
Last Updated:	June 10, 2015
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:


Pulmonary Hypertension Diastolic Heart Failure

Additional relevant MeSH terms:


Hypertension Heart Failure Hypertension, Pulmonary Heart Failure, Diastolic Vascular Diseases	Cardiovascular Diseases Heart Diseases Lung Diseases Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 29, 2016