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Crossover Study From Macitentan or Bosentan Over to Ambrisentan

Phase 4
Terminated
Conditions
Pulmonary Arterial Hypertension
Interventions
Registration Number
NCT02885012
Lead Sponsor
Medical University of South Carolina
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
3
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Switch to Letairis from BosentanAmbrisentanSubjects will be switching treatments from Bosentan (Tracleer) to Ambrisentan (Letairis)
Switch to Letairis from MacitentanAmbrisentanSubjects will be switching treatments from Macitentan (Opsumit) to Ambrisentan (Letairis)
Primary Outcome Measures
NameTimeMethod
Change in Stroke VolumeBaseline and 24 Weeks

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
NameTimeMethod
Change in EmPHasis-10 ScoreBaseline and 24 Weeks

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 BiomarkerBaseline and 12 Weeks

NT-proBNP Biomarker: BNP is released from cardiac cells in response to increased pressure. The higher the value the worse the disease status.

Trial Locations

Locations (2)

Ochsner Medical Center

🇺🇸

New Orleans, Louisiana, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

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