The Effects of Ambrisentan on Exercise Capacity in Fontan Patients

NCT01971580 | Completed Phase 4 Results DMC

• 1 other identifier: IN-US-300-D076
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: Patients with a Fontan type palliation are limited by preload, or the rate at which blood returns to the heart after passively traversing the pulmonary capillary bed. By decreasing pulmonary vascular resistance using an endothelin receptor antagonist, both ventricular filling pressures and volumes will increase with a simultaneous decrease in systemic impedance to flow and decrease in central venous pressures, leading to an improved capacity to increase cardiac output, and thereby an improvement in patient functional status. Patients who are candidates for the study will be randomized to a double-blind single crossover study. Therapy with either ambrisentan or placebo will be continued for 12 weeks, with a 2 week washout period between treatment periods. Subjects will be subjected to a VO2 max test to evaluate exercise capacity at enrolment, and on the last day of each treatment period. As a component of the VO2 max testing the patient's VE, VCO2, VE/VCO2 slope, ventilatory anaerobic threshold (VAT), peak work, efficiency, and other physiologic parameters as typically obtained from cardiopulmonary testing will be assessed. In addition, each patient will be asked to complete an SF-36 quality of life questionnaire at enrollment, and on the last day of each study period.

Conditions

Single Ventricle Fontan Palliation

Outcome Measures

Primary Outcomes (1)

• Change in VO2 Max

  Baseline compared to 12 weeks therapy with either ambrisentan or placebo

Secondary Outcomes (1)

• Quality of Life

  12 weeks

Study Arms (2)

Ambrisentan first, Placebo second

OTHER

These patients will be randomized to have ambrisentan during the first study period, and placebo during the second study period.

Drug: Ambrisentan

Placebo first, Ambrisentan second

OTHER

These patients will be randomized to have placebo during the first study period, and ambrisentan during the second study period.

Drug: Ambrisentan

Interventions

Ambrisentan DRUG

Also known as: Letaris

Ambrisentan first, Placebo second; Placebo first, Ambrisentan second

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients over 18 years of age followed at the Center for Adults with Congenital Heart Disease at Washington University School of Medicine or at Saint Louis Childrens Hospital who have had a Fontan-type of palliation with single ventricular physiology.
• Patients must not within the last year have been treated with an endothelin receptor antagonist, phosphodiesterase 5 antagonist, or prostacyclin analogue.
• Female patients must not be pregnant, and during the study period must be using effective contraception (including barrier method with spermicide, intrauterine device, implanon, oral contraceptives) if fertile.
• In the physicians opinion patients must be able to complete a VO2 max test to achieve an RER of \>1.0
• In the physicians opinion patients must be socially and intellectually able to adhere to the treatment regimen and follow-up
• Patients must be intellectually able to reliably complete an SF-36 questionnaire on quality of life.
• Patients must be clinically stable for at least 3 months prior to enrolment.
• Patients must not have had surgery within 6 months prior to enrolment, and have no planned surgery for the study period.
• Patients must provide informed consent.

You may not qualify if:

• Patients under 18 years of age.
• Patients who are pregnant, nursing, or who in the physician's opinion are likely to become pregnant.
• Patients who are clinically unstable.
• Patients who have previously been treated with either an endothelin receptor antagonist and stopped due to adverse side effects.
• Patients with an AST or ALT of \>3 x normal.
• Patients having any known contraindication to the initiation of ambrisentan.
• Patients with a calculated creatinine clearance of \<60ml/min
• Patients with a serum hemoglobin concentration of \<10mg/dl
• Patients with a poorly controlled cardiac arrhythmia
• Patients who are unable to provide independent informed consent.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Interventions

ambrisentan

Limitations and Caveats

Large dropout rate. Small sample size. Many individuals did not achieve the target RER during cardiopulmonary exercise testing.

Results Point of Contact

• Title: Ari Cedars
• Organization: UT Southwestern

acedars97@gmail.com

3149224788

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: October 29, 2013
• Study Start: August 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 7, 2018
• Results First Posted: May 7, 2018

Record last verified: 2018-05

Locations

US (1)