Crossover Study From Macitentan or Bosentan Over to Ambrisentan (Letairis)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ambrisentan
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of a Connective Tissue Disease (CTD)
- Age range: 18-80 years old
- Previous Right Heart Catheterization (RHC) demonstrating PAH
- Forced vital capacity (FVC) greater than 50%
- Carbon Monoxide Diffusing Capacity (DLCO) greater than 50%
- World Health Organization (WHO) functional class II or III
- Able to perform a 6 minute walk test (6MWT)
- Stable dose of antihypertensive medications
- Non-pregnant females
- Have to be currently on stable dose of bosentan for at least 3 months
- Adequate acoustic images to allow for transthoracic echocardiography to be performed
Exclusion Criteria:
- Exercise limitation related to a non-cardiopulmonary reason (e.g. arthritis)
- Severe systemic hypertension greater than 170/95
- Patients with a prior history of cardiovascular disease
- WHO functional class IV status
- Patients with severe other organ disease felt by investigators to impact on survival during the course of the study.
- FVC less than 50% of predicted
- DLCO less than 50% of predicted
Sites / Locations
- Ochsner Medical Center
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Switch to Letairis from Bosentan
Switch to Letairis from Macitentan
Arm Description
Subjects will be switching treatments from Bosentan (Tracleer) to Ambrisentan (Letairis)
Subjects will be switching treatments from Macitentan (Opsumit) to Ambrisentan (Letairis)
Outcomes
Primary Outcome Measures
Change in Stroke Volume
Echocardiography is used to estimate the stroke volume, or the amount of blood ejected from the heart with each beat. An average over three beats is used for the estimate and is reported as ml/beat.
Secondary Outcome Measures
Change in EmPHasis-10 Score
Questionnaire-. The questionnaire is designed to determine how pulmonary hypertension affects the patient's life by asking 10 questions which address breathlessness, fatigue, control, and confidence. emPHasis-10 consists of 10 items which address breathlessness, fatigue, control and confidence. Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end. A total emPHasis-10 score is derived using simple aggregation of the 10 items. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life.
Disease Status as Measured by Change in Biomarker
NT-proBNP Biomarker: BNP is released from cardiac cells in response to increased pressure. The higher the value the worse the disease status.
Full Information
NCT ID
NCT02885012
First Posted
May 3, 2016
Last Updated
April 5, 2019
Sponsor
Medical University of South Carolina
Collaborators
Ochsner Health System
1. Study Identification
Unique Protocol Identification Number
NCT02885012
Brief Title
Crossover Study From Macitentan or Bosentan Over to Ambrisentan
Acronym
Letairis
Official Title
A Safety and Clinical Efficacy Study Measuring Echocardiographic Composite Comparing Ambrisentan (Letairis®) After a Switch From Bosentan (Tracleer®) or Macintentan (Opsumit®) in Treatment of Pulmonary Arterial Hypertension (PAH)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
Study ending due to lack of enrollment.
Study Start Date
June 2016 (undefined)
Primary Completion Date
July 7, 2017 (Actual)
Study Completion Date
July 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
Collaborators
Ochsner Health System
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to learn more about the safety and effects of switching treatments from bosentan (Tracleer) or macientan (Opsumit) to ambrisentan (Letairis) over 24 weeks in subjects with Connective Tissue Disease associated Pulmonary Arterial Hypertension (CTD-PAH).
Detailed Description
The study will consist of a group of subjects who have been on bosentan for at least three months and a group that has been on macitentan for at least three months. Both groups will be switched to Letairis 5mg daily after the bosentan or macitentan therapy for three months and then increased to a dose of Letairis 10mg daily at week 4 if well tolerated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Switch to Letairis from Bosentan
Arm Type
Experimental
Arm Description
Subjects will be switching treatments from Bosentan (Tracleer) to Ambrisentan (Letairis)
Arm Title
Switch to Letairis from Macitentan
Arm Type
Experimental
Arm Description
Subjects will be switching treatments from Macitentan (Opsumit) to Ambrisentan (Letairis)
Intervention Type
Drug
Intervention Name(s)
Ambrisentan
Other Intervention Name(s)
Letairis
Intervention Description
At entry to the study following the screen visits, patients will be switched from bosentan to ambrisentan to complete a 24 week trial. The only study intervention will be ambrisentan.
Primary Outcome Measure Information:
Title
Change in Stroke Volume
Description
Echocardiography is used to estimate the stroke volume, or the amount of blood ejected from the heart with each beat. An average over three beats is used for the estimate and is reported as ml/beat.
Time Frame
Baseline and 24 Weeks
Secondary Outcome Measure Information:
Title
Change in EmPHasis-10 Score
Description
Questionnaire-. The questionnaire is designed to determine how pulmonary hypertension affects the patient's life by asking 10 questions which address breathlessness, fatigue, control, and confidence. emPHasis-10 consists of 10 items which address breathlessness, fatigue, control and confidence. Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end. A total emPHasis-10 score is derived using simple aggregation of the 10 items. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life.
Time Frame
Baseline and 24 Weeks
Title
Disease Status as Measured by Change in Biomarker
Description
NT-proBNP Biomarker: BNP is released from cardiac cells in response to increased pressure. The higher the value the worse the disease status.
Time Frame
Baseline and 12 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of a Connective Tissue Disease (CTD)
Age range: 18-80 years old
Previous Right Heart Catheterization (RHC) demonstrating PAH
Forced vital capacity (FVC) greater than 50%
Carbon Monoxide Diffusing Capacity (DLCO) greater than 50%
World Health Organization (WHO) functional class II or III
Able to perform a 6 minute walk test (6MWT)
Stable dose of antihypertensive medications
Non-pregnant females
Have to be currently on stable dose of bosentan for at least 3 months
Adequate acoustic images to allow for transthoracic echocardiography to be performed
Exclusion Criteria:
Exercise limitation related to a non-cardiopulmonary reason (e.g. arthritis)
Severe systemic hypertension greater than 170/95
Patients with a prior history of cardiovascular disease
WHO functional class IV status
Patients with severe other organ disease felt by investigators to impact on survival during the course of the study.
FVC less than 50% of predicted
DLCO less than 50% of predicted
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terrill Huggins, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ochsner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Crossover Study From Macitentan or Bosentan Over to Ambrisentan
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