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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00310830
• Date of registration: 03/04/2006
• Prospective Registration: No
• Primary sponsor: Actelion
• Public title: Efficacy and Safety of Bosentan in Sickle Cell Disease (SCD) Patients With Pulmonary Arterial Hypertension (PAH)
• Scientific title: Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Bosentan in Patients With Symptomatic Pulmonary Arterial Hypertension Associated With Sickle Cell Disease
• Date of first enrolment: March 2006
• Target sample size: 14
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00310830
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

France, Netherlands, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria: Screening Criteria:

1. Males or females = 12 years of age with a documented history of SCD

2. Patients with symptomatic PAH 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/ß0 genotype and with Hb A = 10%

2. Six-minute walk test (6MWT) distance = 150 m and = 450 m

3. PAH 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) = 25 mmHg

- Pulmonary capillary wedge pressure (PCWP) = 15 mmHg measured by RHC or left
ventricular end diastolic pressure (LVEDP) = 15 mmHg measured by left heart
catheterization, if PCWP measurement is not reliable

- Pulmonary vascular resistance (PVR) at rest = 160 dyn.sec/cm5

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 < 85 mmHg

3. Uncontrolled hypertension with systolic blood pressure >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. Evidence of cirrhosis or portal hypertension on a liver ultrasound or biopsy

10. ALT = 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



Age minimum: 12 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension

Intervention(s)

Drug: Bosentan

Primary Outcome(s)

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(s)

Time to clinical worsening from Baseline to EOS. [Time Frame: 16 weeks]

Secondary ID(s)

ASSET-1

AC-052-368

Source(s) of Monetary Support

Please refer to primary and secondary sponsors