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Effects of bosentan in a homogeneous population of SSc subjects with a predefined restriction of blood flow in the hands

Phase 4
Completed
Conditions
Systemic Connective Tissue Disease
Systemic Scleroderma
10010761
10047043
10003216
Registration Number
NL-OMON36236
Lead Sponsor
Actelion Pharmaceuticals
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
106
Inclusion Criteria

1. Male and female subjects > 18 years diagnosed with systemic sclerosis;
2. Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to historical healthy controls;
3. Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception;
4. A history of 1 or more DUs within 2 years prior to inclusion;
5. No use of bosentan in the past;
6. Subjects willing and able to sign informed consent.

Exclusion Criteria

1. Parenteral Prostanoid treatment for DU < 3 months ago;
2. Chronic treatment with PDE-5 inhibitor or ERA;
3. History of bosentan use;
4. Irreversible significant limitation of the hand function, e.g. amputation of more than one finger;
5. Other types of system- or connective tissue diseases;
6. Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy;
7. Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months;
8. Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN);
9. Moderate to severe liver function disorder;
10. Pregnancy or breastfeeding;
11. Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors;
12. Hypersensitivity for bosentan or one of its components;
13. Subjects not able to follow the protocol.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>- Relationship between blood flow in the hands, as measured by laser Doppler<br /><br>imaging, and extent of digital ulcera assessed by the mean blood flow<br /><br>restriction in four distinct groups of patients: patients without current<br /><br>digital ulcera (pitting scars allowed), patients with new digital ulcera (less<br /><br>than 3 months old), patients with persistent digital ulcera (more than 3 months<br /><br>old) and patients with significant tip-necrosis;<br /><br><br /><br>- Change in blood flow in the hands after 12 weeks of bosentan treatment<br /><br>compared to the blood flow at 0 weeks, as measured by laser Doppler imaging.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>- Change in blood flow in different regions of the hands after 4 and 12 weeks<br /><br>of bosentan treatment compared to the blood flow after 0 weeks, as measured by<br /><br>laser Doppler imaging;<br /><br><br /><br>- Change in modified Rodnan Skin Score (mRSS) from 0 weeks to 12 weeks, 26<br /><br>weeks and 52 weeks of bosentan treatment;<br /><br><br /><br>- Change in selected components of the Scleroderma Health Assessment<br /><br>Questionnaire from 0 weeks to 12 weeks, 26 weeks and 52 weeks of bosentan<br /><br>treatment;<br /><br><br /><br>- Changes in EQ 5D from 0 weeks to 12 weeks, 26 weeks and 52 weeks of bosentan<br /><br>treatment;<br /><br><br /><br>- Total number of new DU and pitting scars developed from 0 weeks to 12 weeks,<br /><br>26 weeks and 52 weeks of bosentan treatment.</p><br>
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