Bosentan in Systemic Sclerosis

Study Overview
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Brief Summary
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The effect of bosentan on digital ulcers (DU) was studied in two randomized placebo-controlled trials (RAPIDS-1 and RAPIDS-2). A limitation of these studies was the heterogeneous study population. More importantly, there were no endpoints that assessed changes in vasculopathy and / or perfusion. Laser Doppler imaging has been shown to effectively demonstrate blood flow restrictions in the hands of patients with Systemic Sclerosis (SSc). The relation between blood flow restriction in the hands measured by laser Doppler imaging and the extent of DU disease has not been studied. The current study will attempt to demonstrate this relation. In addition, the impact of bosentan on the blood flow in the hands, in a defined cohort of SSc-DU patients with a history of DU within the past 2 years and a clinically relevant reduction of blood flow in the hands, will be assessed.

Official Title
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Effects of Bosentan in a Homogenous Population of Systemic Sclerosis Subjects With a Predefined Restriction of Blood Flow in the Hands

Conditions
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Systemic Sclerosis, Digital Ulcers

Intervention / Treatment
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* Drug: Bosentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects > 18 years diagnosed with SSc; Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to the healthy volunteers; Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception; A history of 1 or more DUs within 2 years prior to inclusion; No use of bosentan in the past; Subjects willing and able to sign informed consent. Exclusion Criteria: Parenteral prostanoid treatment for DU < 3 months ago; Chronic treatment with PDE-5 inhibitor or ERA; History of bosentan use Irreversible significant limitation of the hand function, e.g. amputation of more than one finger; Other types of system- or connective tissue diseases; Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy; Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months; Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN); Moderate to severe liver function disorder; Pregnancy or breastfeeding; Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors; Hypersensitivity for bosentan or one of its components; Subjects not able to follow the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Bosentan<br>* 2 tablets of 62.5 mg a day from baseline to week 4, then 2 tablets of 125 mg per day to week 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean blood flow restriction in patients | Relationship between blood flow in the hands, as measured by laser Doppler imaging, and extent of Digital Ulcer disease assessed by the mean blood flow restriction in four distinct groups of patients: patients without current Digital Ulcers (pitting scars allowed), patients with new Digital Ulcers (< 3 months), patients with persistent Digital Ulcers (> 3 months) and patients with significant tip-necrosis. | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood flow in the hands | Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the baseline, as measured by laser Doppler imaging. | Baseline to 12 weeks of bosentan treatment |