Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients Diagnosed With Pulmonary Hypertension (PH) (ASSET-2)

January 31, 2025 updated by: Actelion

Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Bosentan in Patients With Symptomatic Pulmonary Hypertension Associated With Sickle Cell Disease

The study will assess the effect of bosentan on pulmonary vascular resistance and exercise capacity in Sickle Cell Disease (SCD) patients diagnosed with Pulmonary Hypertension. It consists of 3 phases: screening, treatment and follow-up. During the screening visit, the study doctor will decide if patients meet the study requirements. All potential patients will have a diagnosis of increased pulmonary artery pressures that is shown by right heart catheterization conducted shortly prior to start of study treatment. Patients will be asked to perform exercise capacity test (walking as far as possible for 6 minutes). Following the baseline visit the treatment phase consists of 4 additional clinic visits during which the good and bad effects of the drug are reviewed and exercise capacity test will be repeated. Patients will be treated for 16 weeks. Blood samples will be collected every month, or more often, if needed. At the end of the study some of the patients will be asked to repeat the right heart catheterization. All patients will repeat an exercise capacity test. After completion of the study, patients will have the option of enrolling in a long-term follow-up study where all patients will receive active drug. Patients electing not to participate in the extension study will be followed up for safety assessments for about 28 days after the end of the study treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clamart, France, 92141
        • Hôpital Antoine Béclère
      • Creteil, France, 94010
        • CHU Henri Mondor
    • La Martinique
      • Fort de France, La Martinique, France, 97200
        • CHU de Fort de France
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Amsterdam Medical Center, Department of Hematology
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital, Rheumatology Department
      • Sheffield, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital, Pulmonary Vascular Medicine
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama
    • California
      • Berkeley, California, United States, 94705
        • Alta Bates Medical Center
      • Torrance, California, United States, 90502
        • Harbor -UCLA Medical Center
    • Colorado
      • Denver, Colorado, United States, 80262
        • University of Colorado Health Sciences Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20060
        • Howard University Hospital
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Medical Center
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center/Boston University School of Medicine
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Harper University Hospital/Wayne State University
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital; Dept. of Pulmonology
    • Missouri
      • St. Louis, Missouri, United States, 63104
        • SoLUtions/Saint Louis University
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center; Pediatric Cardiology
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Comprehensive Sickle Cell Program
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center; Duke University Health Systems
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Lung Center
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • University of Tennessee Health Science Center
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital/Baylor College of Medicine; Pulmonary and Critical Care Medicine
      • Houston, Texas, United States, 77030
        • University of Texas Medical School; Division of Pulmonary and Critical Care Medicine
    • Virginia
      • Richmond, Virginia, United States, 23298-5028
        • Virginia Commonwealth University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria: Screening Criteria:

  1. Males or females > or = 12 years of age with a documented history of SCD
  2. Patients with symptomatic PH associated with shortness of breath
  3. Patients with tricuspid regurgitation jet (TRJ) velocity of > 2.9 m/sec based on echo/Doppler conducted within 6 months prior to randomization and not during SCD crisis
  4. Signed written informed consent is obtained from the patient or patient's parent/ legal representative prior to initiation of any study related procedure

Inclusion Criteria:

  1. Patients with hemoglobin (Hb) SS or Hb S/β0 genotype and with Hb A < or = 10%
  2. Six-minute walk test (6MWT) distance > or = 150 m and < or = 450 m

  3. Pulmonary hypertension confirmed by right heart catheterization (RHC) performed at the study site within 3 months of the randomization visit and defined as:

    • Mean pulmonary arterial pressure (mPAP) > or - 25 mmHg
    • Pulmonary capillary wedge pressure (PCWP) measured by right heart catheterization or left ventricular end diastolic pressure (LVEDP) measured by left heart catheterization, if PCWP measurement is not reliable. Two subsets of patients will be considered for this study:
    • PCWP < or = 15 mm Hg, if PVR at rest < 160 dyn.sec/cm5
    • PCWP of 16-25 mm Hg with any PVR value
  4. Women of childbearing potential must have a negative result on their serum pregnancy test and use reliable methods of contraception during study treatment and for 3 months after study treatment termination

Exclusion Criteria:

  1. Left ventricular ejection fraction < 40% (echo/Doppler)
  2. Systolic blood pressure (SBP) < 85 mmHg
  3. Uncontrolled hypertension with SBP > 160 mmHg and/or diastolic blood pressure > 100 mmHg
  4. Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) < 0.5
  5. Total lung capacity (TLC) < 50% of normal predicted value
  6. Significant cardiac disease: ischemic, valvular, constrictive
  7. Hemoglobin concentration < 6.0 g/dL at the time of randomization
  8. Acute liver disease
  9. cirrhosis or portal hypertension
  10. ALT > or = 2 times upper limit of normal (ULN) and/or albumin < 2.8 g/dL
  11. Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication, symptomatic hip osteonecrosis
  12. Vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) within 2 weeks of randomization or more than 12 VOC and/or ACS within the last 12 months
  13. Blood transfusion within 4 weeks prior to randomization
  14. Illness with a life expectancy shorter than 6 months
  15. HIV with opportunistic infection
  16. Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
  17. Pregnant or lactating women
  18. Recently started (< 8 weeks prior to randomization) or planned, exercise-based cardio-pulmonary rehabilitation program
  19. Bone marrow transplantation
  20. Treatment or planned treatment with another investigational drug within 3 months prior to randomization
  21. Treatment for pulmonary hypertension with an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months prior to randomization or with L-arginine within 1 week prior to randomization
  22. Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, amiodarone, miconazole and glibenclamide (glyburide) within 1 week prior to randomization
  23. Known hypersensitivity to bosentan or any of its excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 2
Drug: bosentan
Oral Initial dose: 62.5 mg b.i.d. for 4 weeks for all patients, maintenance dose: 125 mg
No Intervention: 1

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change from Baseline to End of Study in 6MWT distance. A mean difference from placebo of at least 35 m is considered clinically relevant.
Time Frame: 16 weeks
16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Time to clinical worsening from Baseline to End of Study.
Time Frame: 16 weeks
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Actelion

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Irina M Kline, MD, Actelion

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2007

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 10, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2006

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 12, 2006

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AC-052-369
  • ASSET-2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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