Placebo Controlled Trial of Bosentan in Scleroderma Patients
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Placebo Controlled Trial of Bosentan vs Placebo in NYHA Class I/II Scleroderma Patients With Exercise Induced Pulmonary Hypertension|
- Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol. [ Time Frame: This will be determined after 16 weeks on the study medication. ] [ Designated as safety issue: No ]
- 6-minute Walk Distance [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]The distance walked during a 6-minute walk test.
- Brain Natriuretic Peptide (BNP) Level [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Serum BNP level
- Endothelin-1(ET-1) Level [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]From saved serum
- Quality of Life (QOL) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]QOL is measured using the Short Form 36 Health Survey (SF-36, which measures health on eight dimensions: general health perception, physical and social functioning, role limitations by physical or emotional problems, mental health, vitality, and bodily pain. For each dimension items are coded, summed, and transformed on to a scale from 0 (worst health) to 100 (best health).
|Study Start Date:||September 2006|
|Study Completion Date:||March 2010|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
62.5 mg by mouth (PO) twice daily (Bid) for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks
|Placebo Comparator: Placebo||
62.5 mg PO Bid for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks
Pulmonary hypertension (PAH) is a common and usually fatal form of lung disease in systemic sclerosis (SSc). Multiple drugs have been approved for the treatment of New York Heart Association (NYHA)Class III/IV PAH in scleroderma. Bosentan is an endothelin-1 antagonist which showed significant improvement in distance walked during 12 week clinical trials in PAH patients (7). Therapy for asymptomatic systemic sclerosis patients diagnosed incidentally with PAH (World Health Organization (WHO) Functional Class I) remains controversial. We hypothesize that asymptomatic or minimally symptomatic patients with systemic sclerosis and normal resting pulmonary artery pressures who demonstrate an abnormal rise in pulmonary artery systolic pressure with stress Doppler echocardiography testing represent a subset of patients who already have pulmonary vascular disease and who are at risk for the development of severe PAH. We further hypothesize that early identification and treatment of such patients may retard the progression of that disease.
- Stress echocardiography identifies early pulmonary vascular disease by detecting exercise-induced pulmonary hypertension in patients with systemic sclerosis.
- Treatment of exercise-induced PAH with Bosentan will lead to improved exercise endurance in patients with systemic sclerosis.
Subjects will be recruited from those patients who have had an abnormal exercise test as part of an earlier study, Exercise Echocardiograms in Scleroderma (IRB# 03-363).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00377455
|United States, Connecticut|
|University of Connecticut|
|Farmington, Connecticut, United States, 06030|
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|Principal Investigator:||Virginia D Steen, MD||Georgetown University|