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Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by University of Texas Southwestern Medical Center.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Kelly M Chin, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00840463
First received: February 6, 2009
Last updated: September 16, 2013
Last verified: February 2009
History of Changes
  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:

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 ]
Estimated Enrollment: 20
Study Start Date: January 2009
Estimated 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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

Contacts
Contact: Kelly M Chin, MD 214-645-6486 kelly.chin@utsouthwestern.edu
Contact: Fernando Torres, MD 214-645-6487 fernando.torres@utsouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-8550
Contact: Kelly M Chin, MD    214-645-6486    kelly.chin@utsouthwestern.edu   
Contact: Lindsey Vacovsky, MPH    214-645-6488    lindsey.vacovsky@utsouthwestern.edu   
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

No publications provided

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: September 16, 2013
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:
Heart Failure
Hypertension, Pulmonary
Cardiovascular Diseases
 Heart Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on March 03, 2015