Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan

NCT00840463 | Terminated Phase 4 Results DMC

• 1 other identifier: IN-US-300-0126
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Hypertension; Heart Failure With Preserved Ejection Fraction

Keywords

Pulmonary Hypertension; Diastolic Heart Failure

Outcome Measures

Primary Outcomes (2)

• Change in Pulmonary Vascular Resistance (Wood Units)

  The primary efficacy outcome will be Pulmonary Vascular Resistance.PVR will be calculated as \[(PA mean - wedge) / Cardiac Output\]

  Baseline and Four months

• Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs)

  Freedom from clinically significant adverse events will be measure by determining the number free from CSAEs and those who developed CSAEs

  4 months

Secondary Outcomes (3)

• Change in 6 Minute Walk Distance

  Baseline and Four months

• Change in Functional Class

  basline and 4 months

• Change in Short Form-36 Physical Functioning

  baseline 4 months

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: Ambrisentan

2

PLACEBO COMPARATOR

Other: Placebo

Interventions

Ambrisentan DRUG

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).

Also known as: Letairis

1

Placebo OTHER

Sugar pill

Also known as: The placebo will look identical to the Ambrisentan tablets

2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Catheterization
• Elevated pulmonary arterial pressure (PA mean \>25mmHg)
• Elevated pulmonary vascular resistance (\>240 dynes.cm.sec-5) or transpulmonary gradient (\>12 mmHg)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Gilead Sciences: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390-8550, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure, Diastolic

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Failure; Heart Diseases

Results Point of Contact

• Title: Kelly Chin
• Organization: UT Southwestern

kelly.chin@utsouthwestern.edu

214-645-1825

Study Officials

• Kelly M Chin, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Fernando Torres, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: February 10, 2009
• Study Start: January 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: January 1, 2014
• Last Updated: May 19, 2020
• Results First Posted: May 22, 2019

Record last verified: 2020-05

Locations

US (1)