The Effects of Ambrisentan on Exercise Capacity in Fontan Patients

• ClinicalTrials.gov Identifier: NCT01971580
• Recruitment Status: Completed
• First Posted: October 29, 2013
• Results First Posted: May 7, 2018
• Last Update Posted: May 7, 2018
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Ari Cedars, Washington University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Single Ventricle Fontan Palliation	Drug: Ambrisentan	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effects of Ambrisentan on Exercise Capacity in Fontan Patients
• Study Start Date: August 2012
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Ambrisentan first, Placebo second; These patients will be randomized to have ambrisentan during the first study period, and placebo during the second study period.	Drug: Ambrisentan; Other Name: Letaris
Placebo first, Ambrisentan second; These patients will be randomized to have placebo during the first study period, and ambrisentan during the second study period.	Drug: Ambrisentan; Other Name: Letaris

Outcome Measures

Primary Outcome Measures :

1. Change in VO2 Max [ Time Frame: Baseline compared to 12 weeks therapy with either ambrisentan or placebo ]

Secondary Outcome Measures :

1. Quality of Life [ Time Frame: 12 weeks ]
   Change in Rand 36-item Short Form (SF-36) physical function score (0-100). On the Rand SF-36 questionnaire, a score closer to 100 (higher) suggests lesser disability, while a score closer to 0 (lower) suggests more disability.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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.
2. Patients must not within the last year have been treated with an endothelin receptor antagonist, phosphodiesterase 5 antagonist, or prostacyclin analogue.
3. 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.
4. In the physicians opinion patients must be able to complete a VO2 max test to achieve an RER of >1.0
5. In the physicians opinion patients must be socially and intellectually able to adhere to the treatment regimen and follow-up
6. Patients must be intellectually able to reliably complete an SF-36 questionnaire on quality of life.
7. Patients must be clinically stable for at least 3 months prior to enrolment.
8. Patients must not have had surgery within 6 months prior to enrolment, and have no planned surgery for the study period.

9. Patients must provide informed consent.

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Exclusion Criteria:

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

10. Patients who are unable to provide independent informed consent.

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Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

More Information

• Responsible Party: Ari Cedars, Assistant Professor of Medicine, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01971580
• Other Study ID Numbers: IN-US-300-D076
• First Posted: October 29, 2013
• Results First Posted: May 7, 2018
• Last Update Posted: May 7, 2018
• Last Verified: May 2018

Additional relevant MeSH terms:

Ambrisentan; Antihypertensive Agents