Digital Ulcera in Systemic Sclerodermia patients MedDRA version: 12.1 Level: LLT Classification code 10053400 Term: Endothelin increased
Conditions
Sponsors
Actelion Pharmaceuticals Nederland bv
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects > 18 years diagnosed with SSc; 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate the correlation of blood flow in the hands and the extent of DU disease in patients with SSc. - Evaluate the effect of bosentan on the blood flow in the hands from baseline to 12 weeks, measured by laser Doppler imaging, in SSc subjects with a history of DU disease in the past 2 years and clinically relevant reduction of blood flow at baseline.;Secondary Objective: - Evaluate the effect of bosentan on the blood flow in different regions of the hands from baseline to 4 weeks and 12 weeks. -Evaluate the effect of bosentan on the hand function, pain perception and quality of life from baseline to 12 weeks, 26 weeks and 52 weeks. -Evaluate the effect of bosentan on the modified Rodnan skin score from baseline to 12 weeks, 26 weeks and 52 weeks. -Evaluate the effect of bosentan on the development of new digital ulcers and pitting scars from baseline to 12 weeks, 26 weeks and 52 weeks.;Primary end point(s): - Correlation between blood flow in the hands, as measured by laser Doppler imaging, and extent of DU disease assessed by the mean blood flow restriction in four distinct groups of patients: patients without current DU (pitting scars allowed), patients with new DU (3mo) and patients with significant tip-necrosis. - Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the baseline, as measured by laser Doppler imaging. | — |
Countries
Netherlands
Outcome results
None listed