Placebo Controlled Trial of Bosentan in Scleroderma Patients

This study has been terminated.
(Study was terminated due to inadequate enrolment)
Sponsor:
Collaborator:
Actelion
Information provided by:
Georgetown University
ClinicalTrials.gov Identifier:
NCT00377455
First received: September 14, 2006
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Systemic Scleroderma
Pulmonary Hypertension
Drug: Bosentan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 6-minute Walk Distance [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    The distance walked during a 6-minute walk test.

  • Brain Natriuretic Peptide (BNP) Level [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Serum BNP level

  • Endothelin-1(ET-1) Level [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    From saved serum

  • Quality of Life (QOL) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 5
Study Start Date: September 2006
Study Completion Date: March 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00377455

Locations
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
Actelion
Investigators
Principal Investigator: Virginia D Steen, MD Georgetown University
  More Information

Publications:
Responsible Party: Virginia Steen, MD, Georgetown University
ClinicalTrials.gov Identifier: NCT00377455     History of Changes
Other Study ID Numbers: IRB 06-043
Study First Received: September 14, 2006
Results First Received: March 28, 2011
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Georgetown University:
scleroderma
systemic sclerosis
bosentan
pulmonary hypertension
PHAROS
PHROS
exercise echocardiogram

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Hypertension
Hypertension, Pulmonary
Connective Tissue Diseases
Skin Diseases
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014