Protocol Number: 06-H-0124

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 (ASSET 2)

Number:

06-H-0124

Summary:

This study will examine whether the drug bosentan can decrease pulmonary hypertension (PH, high blood pressure in the artery that leads from the heart to the lungs) and improve exercise capability and quality of life in patients with sickle cell disease (SCD) who develop PH. Nearly one-third of patients with SCD develop some form of pulmonary hypertension, which forces the heart to work harder and can cause fatigue, dizziness, and shortness of breath. Bosentan blocks a hormone called endothelin that is increased in SCD. It also improves blood flow in the lungs and the rest of the body, improving PH symptoms.

Patients 16 years and older with SCD and PH may be eligible for this study. Candidates are screened with a medical history, lung function tests, blood test, echocardiogram (heart ultrasound), and measurements of exercise capacity (6-minute walk), body weight, blood pressure and heart rate. Participants undergo the following tests and procedures:

Study day 1

-Physical examination, blood test, electrocardiogram (EKG), evaluation of shortness of breath, 6-minute walk test, pregnancy test for women who can become pregnant.

-Heart catheterization to diagnose and evaluate PAH: A thin plastic tube is placed into a vein in the arm, neck or groin and threaded through the vessel to the heart and the blood vessels going to the lungs. This test checks blood pressure in the heart chambers and blood oxygen level in different parts of the heart and examines the valves between the chambers of the heart. Patients may be sedated for the procedure.

-Medication: Patients are randomly assigned to take either 62.5 mg of bosentan or a placebo in tablet form twice a day.

-Weekly phone calls to check patients' health status between visits.

Week 4 clinic visit

-Increase bosentan to maintenance dose of 125 mg.

-Review health status and medication side effects.

-Measure body weight, blood pressure and heart rate.

-Blood test (blood test repeated at 6 weeks).

Week 8 and 12 clinic visits

-Evaluate shortness of breath and 6-minute walk.

-Measure body weight, blood pressure and heart rate.

-Review health status and medications.

Week 16 clinic visit (or end of study visit if participation ends early)

-Physical examination, blood test, electrocardiogram.

-6-minute walk test, lung function test.

-Measure body weight, blood pressure and heart rate.

-Heart catheterization (first 60 patients only) to measure heart function and blood flow.

-Quality-of-life questionnaire.

-End study medication (bosentan or placebo).

28-day follow-up clinic visit

-Review medication side effects.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Treatment Study

Sickle Cell Anemia

6-Minute Walk

Right Heart Catheterization

Tracleer

Recruitment Keyword(s):

Sickle Cell Anemia

SS

Condition(s):

Hypertension, Pulmonary

Sickle Cell Disease

Investigational Drug(s):

None

Investigational Device(s):

None

Interventions:

Drug: Bosentan

Supporting Site:

Actelion

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):886-95.

Castro O, Hoque M, Brown BD. Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival. Blood. 2003 Feb 15;101(4):1257-61. Epub 2002 Oct 3.

Minter KR, Gladwin MT. Pulmonary complications of sickle cell anemia. A need for increased recognition, treatment, and research. Am J Respir Crit Care Med. 2001 Dec 1;164(11):2016-9. Review. No abstract available.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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