Pulmonary Arterial Hypertension
Conditions
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.
Interventions
DRUGAmbrisentan
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.
Sponsors
Ochsner Health System
Medical University of South Carolina
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stroke Volume | Baseline 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
| Measure | Time frame | Description |
|---|---|---|
| Change in EmPHasis-10 Score | Baseline 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 Biomarker | Baseline 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Switch to Letairis From Bosentan Subjects will be switching treatments from Bosentan (Tracleer) to Ambrisentan (Letairis)
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. | 1 |
| Switch to Letairis From Macitentan Subjects will be switching treatments from Macitentan (Opsumit) to Ambrisentan (Letairis)
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. | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Switch to Letairis From Bosentan | Switch to Letairis From Macitentan | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Continuous | 53 years | 50.5 years | 51.33 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
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.
Time frame: Baseline and 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch to Letairis From Bosentan | Change in Stroke Volume | -2.8 ml/beat | — |
| Switch to Letairis From Macitentan | Change in Stroke Volume | 8.7 ml/beat | Standard Deviation 4.2 |
Secondary
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.
Time frame: Baseline and 24 Weeks
Population: Second patient in second arm did not complete questionnaire in week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Switch to Letairis From Bosentan | Change in EmPHasis-10 Score | 3 units on a scale |
| Switch to Letairis From Macitentan | Change in EmPHasis-10 Score | 4 units on a scale |
Secondary
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.
Time frame: Baseline and 12 Weeks
Population: Neither subject in group 2 completed week 24 assessment for this outcome so we are reporting changes at week 12 compared to baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch to Letairis From Bosentan | Disease Status as Measured by Change in Biomarker | 926 pg/mL | — |
| Switch to Letairis From Macitentan | Disease Status as Measured by Change in Biomarker | -78 pg/mL | Standard Deviation 362 |