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

NCT00313196 | Terminated Phase 3

• 2 other identifiers: AC-052-369ASSET-2
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pulmonary Hypertension

Keywords

Pulmonary Hypertension; Sickle Cell Disease; Sickle cell anemia; bosentan; ASSET; ASSET-2

Outcome Measures

Primary Outcomes (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.

  16 weeks

Secondary Outcomes (1)

• Time to clinical worsening from Baseline to End of Study.

  16 weeks

Study Arms (2)

1

NO INTERVENTION

2

EXPERIMENTAL

Drug: bosentan

Interventions

bosentan DRUG

Oral Initial dose: 62.5 mg b.i.d. for 4 weeks for all patients, maintenance dose: 125 mg

2

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• Barst RJ, Mubarak KK, Machado RF, Ataga KI, Benza RL, Castro O, Naeije R, Sood N, Swerdlow PS, Hildesheim M, Gladwin MT; ASSET study group*. Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010 May;149(3):426-35. doi: 10.1111/j.1365-2141.2010.08097.x. Epub 2010 Feb 17.

  PMID: 20175775 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary; Anemia, Sickle Cell

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Irina M Kline, MD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 10, 2006
• First Posted: April 12, 2006
• Study Start: April 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: August 1, 2007
• Last Updated: February 4, 2025

Record last verified: 2025-01