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Placebo Controlled Trial of Bosentan in Scleroderma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00377455
Recruitment Status : Terminated (Study was terminated due to inadequate enrolment)
First Posted : September 18, 2006
Results First Posted : July 20, 2011
Last Update Posted : May 24, 2018
Information provided by (Responsible Party):
Virginia Steen, MD, Georgetown University

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

Condition or disease Intervention/treatment Phase
Systemic Scleroderma Pulmonary Hypertension Drug: Bosentan Drug: Placebo Phase 2

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.


  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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2006
Actual Primary Completion Date : September 2009
Actual Study Completion Date : March 2010

Arm Intervention/treatment
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

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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 6-minute Walk Distance [ Time Frame: 16 weeks ]
    The distance walked during a 6-minute walk test.

  2. Brain Natriuretic Peptide (BNP) Level [ Time Frame: 16 weeks ]
    Serum BNP level to evaluate Brain Natriuretic Peptide (BNP) level

  3. Endothelin-1(ET-1) Level [ Time Frame: 16 weeks ]
    From saved serum to determine Endothelian-1 (ET-1) levels in patients

  4. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00377455

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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
Sponsors and Collaborators
Georgetown University
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Principal Investigator: Virginia D Steen, MD Georgetown University
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Responsible Party: Virginia Steen, MD, Professor of Medicine, Georgetown University Identifier: NCT00377455    
Other Study ID Numbers: IRB 06-043
Bosentan ( Other Identifier: Georgetown University )
First Posted: September 18, 2006    Key Record Dates
Results First Posted: July 20, 2011
Last Update Posted: May 24, 2018
Last Verified: April 2018
Keywords provided by Virginia Steen, MD, Georgetown University:
systemic sclerosis
pulmonary hypertension
exercise echocardiogram
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action