Crossover Study From Macitentan or Bosentan Over to Ambrisentan

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Ambrisentan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Switch to Letairis from Bosentan<br>Subjects will be switching treatments from Bosentan (Tracleer) to Ambrisentan (Letairis) | Drug: Ambrisentan<br>* 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.<br>* Other names: Letairis;|
| Experimental: Switch to Letairis from Macitentan<br>Subjects will be switching treatments from Macitentan (Opsumit) to Ambrisentan (Letairis) | Drug: Ambrisentan<br>* 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.<br>* Other names: Letairis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 24 Weeks | 
| 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. | Baseline and 12 Weeks |