Efficacy and Safety of Oral Bosentan on Healing/Prevention of Digital (Finger) Ulcers in Patients With Scleroderma

Study Overview
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Brief Summary
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In an earlier clinical trial, RAPIDS-1, conducted in scleroderma patients with or without digital ulcers at baseline, bosentan significantly reduced the number of new digital ulcers versus placebo. The purpose of the present trial (RAPIDS-2) is to evaluate the prevention and healing effects of bosentan versus placebo on digital ulcers over a 24-week treatment period.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis

Conditions
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Digital Ulcers, Systemic Sclerosis

Intervention / Treatment
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* Drug: Bosentan 62.5 mg
* Drug: Bosentan 125 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Systemic Sclerosis (SSc), diffuse or limited. SSc patients with at least one digital ulcer at baseline qualifying as a cardinal ulcer. Main Exclusion Criteria: Digital ulcers due to conditions other than SSc. Severe pulmonary arterial hypertension (PAH) (Who class III and IV). Malabsorption or any severe organ failure (e.g., lung, kidney, liver) or any life-threatening condition. Treatment with parenteral prostanoids (prostaglandin E, epoprostenol, or prostacyclin analogs) during the past 3 months prior to randomization. Treatment with inhaled or oral prostanoids one month prior to randomization. Previous treatment with bosentan.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bosentan<br>The patients received bosentan 62.5 mg twice daily (b.i.d.) for 4 weeks and then 125 mg b.i.d. for 20 weeks | Drug: Bosentan 62.5 mg<br>* Oral tablets containing 62.5 mg of bosentan<br>* Other names: Ro 47-0203;Drug: Bosentan 125 mg<br>* Oral tablets containing 125 mg of bosentan<br>* Other names: Ro 47-0203;|
| Placebo Comparator: Placebo<br>The patients received the matching placebo for 24 weeks | Drug: Placebo<br>* Oral tablets matching bosentan 62.5-mg tablets and bosentan 125-mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete healing of the cardinal ulcer (CU) up to Week 24 in patients with CU healing maintained for 12 weeks |  | 24 weeks | 
| Total number of new digital ulcers per patient up to Week 24 |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 24 in hand pain | Pain assessed on visual analog scales | Baseline and Week 24 | 
| Change from baseline to Week 24 in hand disability | Hand disability indexed assessed using the Health Assessment Questionaire (HAQ) | Baseline and Week 24 | 
| Proportion of subjects with treatment-emergent adverse events |  | up to 32 weeks (8 week post-treatment follow-up) | 
| Proportion of subjects with liver function abnormalities | Increase in aminotransferases | Every 4 weeks up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scleroderma, Finger Ulcers, Digital Ulcers, Systemic Sclerosis