- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00313196
Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients Diagnosed With Pulmonary Hypertension (PH) (ASSET-2)
January 11, 2012 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
Study Type
Interventional
Enrollment (Actual)
12
Phase
- 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
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Clamart, France, 92141
- Hopital Antoine Beclere
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Creteil, France, 94010
- CHU Henri Mondor
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La Martinique
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Fort de France, La Martinique, France, 97200
- CHU de Fort de France
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Amsterdam, Netherlands, 1105 AZ
- Amsterdam Medical Center, Department of Hematology
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London, United Kingdom, NW3 2QG
- Royal Free Hospital, Rheumatology Department
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Sheffield, United Kingdom, S10 2JF
- Royal Hallamshire Hospital, Pulmonary Vascular Medicine
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama
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California
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Berkeley, California, United States, 94705
- Alta Bates Medical Center
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Torrance, California, United States, 90502
- Harbor -UCLA Medical Center
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Colorado
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Denver, Colorado, United States, 80262
- University of Colorado Health Sciences Center
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District of Columbia
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Washington, District of Columbia, United States, 20060
- Howard University Hospital
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Illinois
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Chicago, Illinois, United States, 60612
- University of Illinois Medical Center
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health
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Massachusetts
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Boston, Massachusetts, United States, 02118
- Boston Medical Center/Boston University School of Medicine
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Michigan
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Detroit, Michigan, United States, 48201
- Harper University Hospital/Wayne State University
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Detroit, Michigan, United States, 48202
- Henry Ford Hospital; Dept. of Pulmonology
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Missouri
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St. Louis, Missouri, United States, 63104
- SoLUtions/Saint Louis University
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center; Pediatric Cardiology
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- UNC Comprehensive Sickle Cell Program
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Durham, North Carolina, United States, 27710
- Duke University Medical Center; Duke University Health Systems
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals of Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19140
- Temple University Lung Center
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Tennessee
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Memphis, Tennessee, United States, 38163
- University of Tennessee Health Science Center
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Texas
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Houston, Texas, United States, 77030
- The Methodist Hospital/Baylor College of Medicine; Pulmonary and Critical Care Medicine
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Houston, Texas, United States, 77030
- University of Texas Medical School; Division of Pulmonary and Critical Care Medicine
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Virginia
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Richmond, Virginia, United States, 23298-5028
- Virginia Commonwealth University Medical Center
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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
Ages Eligible for Study
12 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria: Screening Criteria:
- Males or females > or = 12 years of age with a documented history of SCD
- Patients with symptomatic PH associated with shortness of breath
- 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
- 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:
- Patients with hemoglobin (Hb) SS or Hb S/β0 genotype and with Hb A < or = 10%
- Six-minute walk test (6MWT) distance > or = 150 m and < or = 450 m
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
- 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:
- Left ventricular ejection fraction < 40% (echo/Doppler)
- Systolic blood pressure (SBP) < 85 mmHg
- Uncontrolled hypertension with SBP > 160 mmHg and/or diastolic blood pressure > 100 mmHg
- Forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) < 0.5
- Total lung capacity (TLC) < 50% of normal predicted value
- Significant cardiac disease: ischemic, valvular, constrictive
- Hemoglobin concentration < 6.0 g/dL at the time of randomization
- Acute liver disease
- cirrhosis or portal hypertension
- ALT > or = 2 times upper limit of normal (ULN) and/or albumin < 2.8 g/dL
- 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
- 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
- Blood transfusion within 4 weeks prior to randomization
- Illness with a life expectancy shorter than 6 months
- HIV with opportunistic infection
- Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
- Pregnant or lactating women
- Recently started (< 8 weeks prior to randomization) or planned, exercise-based cardio-pulmonary rehabilitation program
- Bone marrow transplantation
- Treatment or planned treatment with another investigational drug within 3 months prior to randomization
- 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
- Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, amiodarone, miconazole and glibenclamide (glyburide) within 1 week prior to randomization
- 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 |
Intervention / Treatment |
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Experimental: 2
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Oral Initial dose: 62.5 mg b.i.d. for 4 weeks for all patients, maintenance dose: 125 mg
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No Intervention: 1
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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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
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16 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Time to clinical worsening from Baseline to End of Study.
Time Frame: 16 weeks
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16 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- 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.
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
April 1, 2006
Primary Completion (Actual)
August 1, 2007
Study Completion (Actual)
August 1, 2007
Study Registration Dates
First Submitted
April 10, 2006
First Submitted That Met QC Criteria
April 10, 2006
First Posted (Estimate)
April 12, 2006
Study Record Updates
Last Update Posted (Estimate)
January 16, 2012
Last Update Submitted That Met QC Criteria
January 11, 2012
Last Verified
January 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Anemia
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Hemoglobinopathies
- Hypertension
- Anemia, Sickle Cell
- Hypertension, Pulmonary
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Endothelin Receptor Antagonists
- Bosentan
Other Study ID 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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