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

NCT ID: NCT00313196

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2007-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: NO_INTERVENTION

No interventions assigned to this group

2

Group Type: EXPERIMENTAL

bosentan

Intervention Type: DRUG

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

Interventions

bosentan

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Actelion

Principal Investigators

Irina M Kline, MD

Role: STUDY_DIRECTOR

Actelion

References

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.

Reference Type: DERIVED

PMID: 20175775 (View on PubMed)

Other Identifiers

ASSET-2

Identifier Type: -

Identifier Source: secondary_id

AC-052-369

Identifier Type: -

Identifier Source: org_study_id

NCT00307372

Identifier Type: -

Identifier Source: nct_alias