Systemic SclerodermaPhase 2NCT00377455
Placebo Controlled Trial of Bosentan in Scleroderma Patients
A Phase 2 study testing Bosentan in people with Systemic Scleroderma and Pulmonary Hypertension, run by Georgetown University at 2 sites in United States.
Trial summary
The purpose of this study is to determine whether the drug Bosentan improves exercise tolerance in scleroderma patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Scleroderma, Pulmonary Hypertension
- What is being tested?
- Bosentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2006to Mar 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Normal Mean Pulmonary Arterial Pressure (PAP) at rest
- Mean PAP > 30 with exercise
- Wedge Pressure < 18
- Entry criteria for participating in the exercise echocardiogram study (Georegtown IRB 03-363)
Show all 9Show fewer
- Diffusing Capacity (DLCO) <60 with a Forced Vital Capacity (FVC) >60%, or
- FVC/DLCO > 1.6, or
- a resting Pulmonary Arterial Systolic Pressure (PASP)> 40mmHg
Who cannot join
- Established resting pulmonary hypertension
- Congestive heart failure
- Diastolic dysfunction
- Pregnancy
- Inability to adequately walk/exercise
- Severe liver disease
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Connecticut
Farmington, Connecticut, 06030
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
Official title: 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.
Read the 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:
- Stress echocardiography identifies early pulmonary vascular disease by detecting exercise-induced pulmonary hypertension in patients with systemic sclerosis.
- 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).
- Conditions
- Systemic Scleroderma, Pulmonary Hypertension
- Being tested
- Bosentan, Placebo
- Keywords
- scleroderma, systemic sclerosis, bosentan, pulmonary hypertension, PHAROS, PHROS, exercise echocardiogram
- Medical subject headings
- Scleroderma, Systemic, Hypertension, Pulmonary, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
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
PlaceboDrug
62.5 mg PO Bid for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Bosentan | Experimental | Not described Receives: Drug: Bosentan |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: This will be determined after 16 weeks on the study medication.
Secondary outcomes (4)
6-minute Walk Distance
The distance walked during a 6-minute walk test.
Measured: 16 weeks
Brain Natriuretic Peptide (BNP) Level
Serum BNP level to evaluate Brain Natriuretic Peptide (BNP) level
Measured: 16 weeks
Endothelin-1(ET-1) Level
From saved serum to determine Endothelian-1 (ET-1) levels in patients
Measured: 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).
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2006 (estimated)
- Study startSep 2006
- Primary completionSep 2009
- Study completionMar 2010
Why it stopped: Study was terminated due to inadequate enrolment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerodermaStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Actelion
- Responsible party
- Principal investigator, Virginia Steen, MD, Georgetown University
- Investigators
- Virginia D Steen, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00377455
- Sponsor's protocol ID
- IRB 06-043
- Other IDs
- Bosentan
- Status last verified
- Apr 2018
- First submitted
- 14 Sep 2006
- Last updated
- 24 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 3707629Yousem 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.
PubMed 2186993al-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.
PubMed 2585400MacGregor 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.
PubMed 11312386Grunig 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.
PubMed 10973844Steen 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.
PubMed 12571862Rubin 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.
PubMed 11907289
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo Controlled Trial of Bosentan vs Placebo in NYHA Class I/II Scleroderma Patients With Exercise Induced Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT00377455
- Acronym / sponsor ID
- IRB 06-043
- Conditions
- Systemic Scleroderma, Pulmonary Hypertension
- Keywords
- scleroderma, systemic sclerosis, bosentan, pulmonary hypertension, PHAROS, PHROS, exercise echocardiogram
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to inadequate enrolment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Actelion
- Study start
- Sep 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 18 Sep 2006 (estimated)
- Results
- Posted 20 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Stress echocardiography identifies early pulmonary vascular disease by detecting exercise-induced pulmonary hypertension in patients with systemic sclerosis.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bosentan | Experimental | Drug: Bosentan |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (6 listed)
- Established resting pulmonary hypertension
- Congestive heart failure
- Diastolic dysfunction
- Pregnancy
- Inability to adequately walk/exercise
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bosentan62.5 mg by mouth (PO) twice daily (Bid) for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks | Drug | Bosentan |
| Placebo62.5 mg PO Bid for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks | Drug | Placebo |
Primary outcome
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.
4 secondary outcomes
6-minute Walk Distance
Time frame: 16 weeks
Brain Natriuretic Peptide (BNP) Level
Time frame: 16 weeks
Endothelin-1(ET-1) Level
Time frame: 16 weeks
Quality of Life (QOL)
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3707629Stupi 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.
- Background: PubMed 2186993Yousem 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.
- Background: PubMed 2585400al-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.
- Background: PubMed 11312386MacGregor 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.
- Background: PubMed 10973844Grunig 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.
- Background: PubMed 12571862Steen 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.
- Background: PubMed 11907289Rubin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Virginia D Steen, MD principal investigator
Georgetown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bosentan in people with Systemic Scleroderma and Pulmonary Hypertension, run by Georgetown University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00377455, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2018.