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)
3
Enrollment
2
Locations
2
Arms
13.2
Duration (Months)
1.5
Patients Per Site
0.1
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Ochsner Medical CenterNew OrleansLouisianaUnited States70121
    2Medical University of South CarolinaCharlestonSouth CarolinaUnited States29425

    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)

    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:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleSwitch to Letairis From BosentanSwitch to Letairis From Macitentan
    Arm/Group DescriptionSubjects 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
    STARTED12
    COMPLETED12
    NOT COMPLETED00

    Baseline Characteristics

    Arm/Group TitleSwitch to Letairis From BosentanSwitch to Letairis From MacitentanTotal
    Arm/Group DescriptionSubjects 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 Participants123
    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
    TitleChange in Stroke Volume
    DescriptionEchocardiography 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 FrameBaseline and 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSwitch to Letairis From BosentanSwitch to Letairis From Macitentan
    Arm/Group DescriptionSubjects 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 Participants12
    Mean (Standard Deviation) [ml/beat]
    -2.8
    (NA)
    8.7
    (4.2)
    2. Secondary Outcome
    TitleChange in EmPHasis-10 Score
    DescriptionQuestionnaire-. 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 FrameBaseline and 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    Second patient in second arm did not complete questionnaire in week 24
    Arm/Group TitleSwitch to Letairis From BosentanSwitch to Letairis From Macitentan
    Arm/Group DescriptionSubjects 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 Participants11
    Mean (Standard Deviation) [units on a scale]
    3
    (NA)
    4
    (NA)
    3. Secondary Outcome
    TitleDisease Status as Measured by Change in Biomarker
    DescriptionNT-proBNP Biomarker: BNP is released from cardiac cells in response to increased pressure. The higher the value the worse the disease status.
    Time FrameBaseline 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 TitleSwitch to Letairis From BosentanSwitch to Letairis From Macitentan
    Arm/Group DescriptionSubjects 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 Participants12
    Mean (Standard Deviation) [pg/mL]
    926
    (NA)
    -78
    (362)

    Adverse Events

    Time Frame24 Weeks
    Adverse Event Reporting Description
    Arm/Group TitleSwitch to Letairis From BosentanSwitch to Letairis From Macitentan
    Arm/Group DescriptionSubjects 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 BosentanSwitch to Letairis From Macitentan
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/1 (0%) 0/2 (0%)
    Serious Adverse Events
    Switch to Letairis From BosentanSwitch to Letairis From Macitentan
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/1 (0%) 0/2 (0%)
    Other (Not Including Serious) Adverse Events
    Switch to Letairis From BosentanSwitch to Letairis From Macitentan
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/1 (100%) 0/2 (0%)
    Respiratory, thoracic and mediastinal disorders
    Worsening hypoxemia due to pneumonia treated with a Z-pack1/1 (100%) 10/2 (0%) 0
    Chest pain and worsening PAH0/1 (0%) 00/2 (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.

    Results Point of Contact

    Name/TitleJohn Terrill Huggins
    OrganizationMedical University of South Carolina
    Phone(843) 792-2296
    Emailhugginjt@musc.edu
    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