Crossover Study From Macitentan or Bosentan Over to Ambrisentan (Letairis)

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)

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).

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Ambrisentan

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Switch to Letairis from Bosentan; Subjects will be switching treatments from Bosentan (Tracleer) to Ambrisentan (Letairis)	Drug: Ambrisentan; 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.; Other Names: Letairis
EXPERIMENTAL: Switch to Letairis from Macitentan; Subjects will be switching treatments from Macitentan (Opsumit) to Ambrisentan (Letairis)	Drug: Ambrisentan; 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.; Other Names: Letairis

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Ochsner Health System
• Investigators: Principal Investigator: Terrill Huggins, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (ACTUAL): July 7, 2017
• Study Completion (ACTUAL): July 7, 2017

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: August 25, 2016
• First Posted (ESTIMATE): August 31, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 5, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Ambrisentan
• Other Study ID Numbers: 00046009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO