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| ID | Type | Description | Link |
|---|---|---|---|
| Bosentan | Other Identifier | Georgetown University |
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Study was terminated due to inadequate enrolment
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| Name | Class |
|---|---|
| Actelion | INDUSTRY |
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The purpose of this study is to determine whether the drug Bosentan improves exercise tolerance in scleroderma patients.
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:
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bosentan | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bosentan | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 6-minute Walk Distance | The distance walked during a 6-minute walk test. | 16 weeks |
| Brain Natriuretic Peptide (BNP) Level | Serum BNP level to evaluate Brain Natriuretic Peptide (BNP) level |
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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
Entry criteria for participating in the exercise echocardiogram study (Georegtown IRB 03-363)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Virginia D Steen, MD | Georgetown University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Connecticut | Farmington | Connecticut | 06030 | United States | ||
| Georgetown University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3707629 | Background | Stupi AM, Steen VD, Owens GR, Barnes EL, Rodnan GP, Medsger TA Jr. Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis. Arthritis Rheum. 1986 Apr;29(4):515-24. doi: 10.1002/art.1780290409. | |
| 2186993 | Background | Yousem SA. The pulmonary pathologic manifestations of the CREST syndrome. Hum Pathol. 1990 May;21(5):467-74. doi: 10.1016/0046-8177(90)90002-m. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bosentan and Placebo Arms | This group consists of subjects on both arms of the study - bosentan and placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Bosentan and Placebo Arms | This group consists of subjects on both arms of the study - bosentan and placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol. | 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. | Posted | This will be determined after 16 weeks on the study medication. |
|
|
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Serious or Other (non-serious) Adverse Events were collected/assessed, but none observed
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bosentan and Placebo Arms | This group consists of subjects on both arms of the study - bosentan and placebo |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Virginia Steen | Georgetown University | 202-444-6200 | steenv@georgetown.edu |
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| ID | Term |
|---|---|
| D012595 | Scleroderma, Systemic |
| D006976 | Hypertension, Pulmonary |
| D045743 | Scleroderma, Diffuse |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D000077300 | Bosentan |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Placebo | Drug | 62.5 mg PO Bid for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks |
|
| 16 weeks |
| Endothelin-1(ET-1) Level | From saved serum to determine Endothelian-1 (ET-1) levels in patients | 16 weeks |
| Quality of Life (QOL) | 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 |
| Washington D.C. |
| District of Columbia |
| 20007 |
| United States |
| 2585400 | Background | al-Sabbagh MR, Steen VD, Zee BC, Nalesnik M, Trostle DC, Bedetti CD, Medsger TA Jr. Pulmonary arterial histology and morphometry in systemic sclerosis: a case-control autopsy study. J Rheumatol. 1989 Aug;16(8):1038-42. |
| 11312386 | Background | MacGregor AJ, Canavan R, Knight C, Denton CP, Davar J, Coghlan J, Black CM. Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology (Oxford). 2001 Apr;40(4):453-9. doi: 10.1093/rheumatology/40.4.453. |
| 10973844 | Background | Grunig E, Janssen B, Mereles D, Barth U, Borst MM, Vogt IR, Fischer C, Olschewski H, Kuecherer HF, Kubler W. Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Circulation. 2000 Sep 5;102(10):1145-50. doi: 10.1161/01.cir.102.10.1145. |
| 12571862 | Background | Steen V, Medsger TA Jr. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum. 2003 Feb;48(2):516-22. doi: 10.1002/art.10775. |
| 11907289 | Background | Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, Landzberg M, Simonneau G. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002 Mar 21;346(12):896-903. doi: 10.1056/NEJMoa012212. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Secondary | 6-minute Walk Distance | The distance walked during a 6-minute walk test. | Outcomes not available, due to early termination of study | Posted | 16 weeks |
|
|
| Secondary | Brain Natriuretic Peptide (BNP) Level | Serum BNP level to evaluate Brain Natriuretic Peptide (BNP) level | Outcomes not available, due to early termination of study | Posted | 16 weeks |
|
|
| Secondary | Endothelin-1(ET-1) Level | From saved serum to determine Endothelian-1 (ET-1) levels in patients | Outcomes not available, due to early termination of study | Posted | 16 weeks |
|
|
| Secondary | Quality of Life (QOL) | 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). | Outcomes not available, due to early termination of study | Posted | 16 weeks |
|
|
| 0 |
| 5 |
| 0 |
| 5 |
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| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |