- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01971580
The Effects of Ambrisentan on Exercise Capacity in Fontan Patients
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
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Exclusion Criteria:
- 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.
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Ambrisentan first, Placebo second
These patients will be randomized to have ambrisentan during the first study period, and placebo during the second study period.
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Other Names:
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Other: Placebo first, Ambrisentan second
These patients will be randomized to have placebo during the first study period, and ambrisentan during the second study period.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in VO2 Max
Time Frame: Baseline compared to 12 weeks therapy with either ambrisentan or placebo
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Baseline compared to 12 weeks therapy with either ambrisentan or placebo
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life
Time Frame: 12 weeks
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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.
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12 weeks
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IN-US-300-D076
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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