Placebo Controlled Trial of Bosentan in Scleroderma Patients

April 26, 2018 updated by: Virginia Steen, MD, Georgetown University

Placebo Controlled Trial of Bosentan vs Placebo in NYHA Class I/II Scleroderma Patients With Exercise Induced Pulmonary Hypertension

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
62.5 mg PO Bid for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks
Experimental: Bosentan
Drug: Bosentan
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
This will be determined after 16 weeks on the study medication.

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Collaborators

Actelion

Investigators

  • Principal Investigator: Virginia D Steen, MD, Georgetown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

September 14, 2006

First Submitted That Met QC Criteria

September 14, 2006

First Posted (Estimate)

September 18, 2006

Study Record Updates

Last Update Posted (Actual)

May 24, 2018

Last Update Submitted That Met QC Criteria

April 26, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB 06-043
  • Bosentan (Other Identifier: Georgetown University)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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