Placebo Controlled Trial of Bosentan vs Placebo in NYHA Class I/II Scleroderma Patients With Exercise Induced Pulmonary Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol.
研究概览
简要总结
The purpose of this study is to determine whether the drug Bosentan improves exercise tolerance in scleroderma patients.
详细描述
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.
Hypotheses:
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SSc patients > 18 with NYHA functional Class I/II symptoms, informed consent, and who are willing to participate in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) long term study (Georgetown IRB 04-227)
- •Right heart catheterization with
- •Normal Mean Pulmonary Arterial Pressure (PAP) at rest
- •Mean PAP > 30 with exercise
- •Wedge Pressure < 18
- •Entry criteria for participating in the exercise echocardiogram study (Georegtown IRB 03-363)
- •Diffusing Capacity (DLCO) <60 with a Forced Vital Capacity (FVC) >60%, or
- •FVC/DLCO > 1.6, or
- •a resting Pulmonary Arterial Systolic Pressure (PASP)> 40mmHg
排除标准
- •Established resting pulmonary hypertension
- •Congestive heart failure
- •Diastolic dysfunction
- •Pregnancy
- •Inability to adequately walk/exercise
- •Severe liver disease
研究组 & 干预措施
Bosentan
干预措施: Bosentan (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol.
时间窗: This will be determined after 16 weeks on the study medication.
The total exercise time measured using the exercise echocardiogram is evaluated with the standard Bruce Stress Protocol, and this will be determined after 16 weeks on the study medication.
次要结局
- 6-minute Walk Distance(16 weeks)
- Brain Natriuretic Peptide (BNP) Level(16 weeks)
- Endothelin-1(ET-1) Level(16 weeks)
- Quality of Life (QOL)(16 weeks)
研究者
Virginia Steen, MD
Professor of Medicine
Georgetown University