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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00313196
Recruitment Status : Terminated (Slow enrollment)
First Posted : April 12, 2006
Last Update Posted : January 16, 2012
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: bosentan Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : April 2006
Primary Completion Date : August 2007
Study Completion Date : August 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Bosentan
U.S. FDA Resources

Arm Intervention/treatment
No Intervention: 1
Experimental: 2 Drug: bosentan
Oral Initial dose: 62.5 mg b.i.d. for 4 weeks for all patients, maintenance dose: 125 mg

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Time to clinical worsening from Baseline to End of Study. [ Time Frame: 16 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00313196

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Sponsors and Collaborators
Study Director: Irina M Kline, MD Actelion

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Sebastien Roux, MD, Actelion Identifier: NCT00313196     History of Changes
Obsolete Identifiers: NCT00307372
Other Study ID Numbers: AC-052-369
First Posted: April 12, 2006    Key Record Dates
Last Update Posted: January 16, 2012
Last Verified: January 2012

Keywords provided by Actelion:
Pulmonary Hypertension
Sickle Cell Disease
Sickle cell anemia

Additional relevant MeSH terms:
Hypertension, Pulmonary
Anemia, Sickle Cell
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action