Placebo Controlled Trial of Bosentan in Scleroderma Patients

Phase 2

Terminated

• Conditions: Systemic Scleroderma; Pulmonary Hypertension
• Interventions: Drug: Placebo; Drug: Bosentan

• Registration Number: NCT00377455
• Lead Sponsor: Georgetown University

Brief Summary

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

Detailed 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).

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-09-14
• Study First Submitted QC: 2006-09-14
• Study First Posted: 2006-09-18
• Primary Completion: 2009-09
• Study Completion: 2010-03
• Results First Submitted: 2011-03-28
• Results First Submitted QC: 2011-06-21
• Results First Posted: 2011-07-20
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-26
• Last Update Posted: 2018-05-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Bosentan	Bosentan	-

Primary Outcome Measures

Name	Time	Method
Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol.	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.

Secondary Outcome Measures

Name	Time	Method
6-minute Walk Distance	16 weeks	The distance walked during a 6-minute walk test.
Brain Natriuretic Peptide (BNP) Level	16 weeks	Serum BNP level to evaluate Brain Natriuretic Peptide (BNP) level
Endothelin-1(ET-1) Level	16 weeks	From saved serum to determine Endothelian-1 (ET-1) levels in patients
Quality of Life (QOL)	16 weeks	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).

Trial Locations

Locations (2)

University of Connecticut; 🇺🇸 Farmington, Connecticut, United States

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States