Placebo Controlled Trial of Bosentan in Scleroderma Patients

Georgetown University

Status and phase: Terminated; Phase 2

Conditions: Pulmonary Hypertension; Systemic Scleroderma

Treatments: Drug: Placebo; Drug: Bosentan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00377455

Bosentan (Other Identifier)

IRB 06-043

Details and patient eligibility

About

The purpose of this study is to determine whether the drug Bosentan improves exercise tolerance in scleroderma patients.

Full description

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:

1. Stress echocardiography identifies early pulmonary vascular disease by detecting exercise-induced pulmonary hypertension in patients with systemic sclerosis.
2. 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).

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

  1. Normal Mean Pulmonary Arterial Pressure (PAP) at rest
  2. Mean PAP > 30 with exercise
  3. Wedge Pressure < 18

• Entry criteria for participating in the exercise echocardiogram study (Georegtown IRB 03-363)

  1. Diffusing Capacity (DLCO) <60 with a Forced Vital Capacity (FVC) >60%, or
  2. FVC/DLCO > 1.6, or
  3. a resting Pulmonary Arterial Systolic Pressure (PASP)> 40mmHg

Exclusion criteria

• Established resting pulmonary hypertension
• Congestive heart failure
• Diastolic dysfunction
• Pregnancy
• Inability to adequately walk/exercise
• Severe liver disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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5 participants in 2 patient groups, including a placebo group

Bosentan

Experimental group

Treatment:

Drug: Bosentan

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo