Letairis: Crossover Study From Macitentan or Bosentan Over to Ambrisentan

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02885012
• Collaborator: Ochsner Health System (Other)
• Enrollment: 3
• Locations: 2
• Arms: 2
• Duration (Months): 13.2
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Ambrisentan	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jun 1, 2016
• Actual Primary Completion Date: Jul 7, 2017
• Actual Study Completion Date: Jul 7, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
2	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• Ochsner Health System

Investigators

• Principal Investigator: Terrill Huggins, MD, Medical University of South Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 18, 2016

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02885012
• Other Study ID Numbers: 00046009
• First Posted: Aug 31, 2016
• Last Update Posted: Apr 8, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Ambrisentan

Study Results

Participant Flow

Arm/Group Title	Switch to Letairis From Bosentan	Switch to Letairis From Macitentan
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	1	2
COMPLETED	1	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Switch to Letairis From Bosentan	Switch to Letairis From Macitentan	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	1	2	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	2 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53	50.5	51.33
Sex: Female, Male (Count of Participants)
Female	1 100%	2 100%	3 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	2 100%	3 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 100%	2 100%	3 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	1 100%	2 100%	3 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Switch to Letairis From Bosentan	Switch to Letairis From Macitentan
Arm/Group Description	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.	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.
Measure Participants	1	2
Mean (Standard Deviation) [ml/beat]	-2.8 (NA)	8.7 (4.2)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Second patient in second arm did not complete questionnaire in week 24

Arm/Group Title	Switch to Letairis From Bosentan	Switch to Letairis From Macitentan
Arm/Group Description	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.	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.
Measure Participants	1	1
Mean (Standard Deviation) [units on a scale]	3 (NA)	4 (NA)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Neither subject in group 2 completed week 24 assessment for this outcome so we are reporting changes at week 12 compared to baseline.

Arm/Group Title	Switch to Letairis From Bosentan	Switch to Letairis From Macitentan
Arm/Group Description	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.	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.
Measure Participants	1	2
Mean (Standard Deviation) [pg/mL]	926 (NA)	-78 (362)

Adverse Events

Time Frame	24 Weeks
Arm/Group Title	Switch to Letairis From Bosentan		Switch to Letairis From Macitentan
Arm/Group Description	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.		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.
All Cause Mortality
	Switch to Letairis From Bosentan		Switch to Letairis From Macitentan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Serious Adverse Events
	Switch to Letairis From Bosentan		Switch to Letairis From Macitentan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Switch to Letairis From Bosentan		Switch to Letairis From Macitentan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Worsening hypoxemia due to pneumonia treated with a Z-pack	1/1 (100%)	1	0/2 (0%)	0
Chest pain and worsening PAH	0/1 (0%)	0	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.