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The Effects of Ambrisentan on Exercise Capacity in Fontan Patients

Primary Purpose

Single Ventricle Fontan Palliation

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ambrisentan
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Single Ventricle Fontan Palliation

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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.

    -

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.

    -

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Ambrisentan first, Placebo second

Placebo first, Ambrisentan second

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in VO2 Max

Secondary Outcome Measures

Quality of Life
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.

Full Information

First Posted
October 23, 2013
Last Updated
May 4, 2018
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01971580
Brief Title
The Effects of Ambrisentan on Exercise Capacity in Fontan Patients
Official Title
The Effects of Ambrisentan on Exercise Capacity in Fontan Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Single Ventricle Fontan Palliation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ambrisentan first, Placebo second
Arm Type
Other
Arm Description
These patients will be randomized to have ambrisentan during the first study period, and placebo during the second study period.
Arm Title
Placebo first, Ambrisentan second
Arm Type
Other
Arm Description
These patients will be randomized to have placebo during the first study period, and ambrisentan during the second study period.
Intervention Type
Drug
Intervention Name(s)
Ambrisentan
Other Intervention Name(s)
Letaris
Primary Outcome Measure Information:
Title
Change in VO2 Max
Time Frame
Baseline compared to 12 weeks therapy with either ambrisentan or placebo
Secondary Outcome Measure Information:
Title
Quality of Life
Description
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.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. - 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. -
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

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The Effects of Ambrisentan on Exercise Capacity in Fontan Patients

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