Effect of Bosentan in Scleroderma Renal Crisis

Study Overview
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Brief Summary
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Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive collagen deposition, autoimmunity and by vascular hyper-reactivity and obliterative microvascular phenomena that involves multiple organs. Scleroderma Renal Crisis (SRC) occurs in 5% of patients and mainly with diffuse cutaneous SSc. The routine use of angiotensin-converting enzyme inhibitors (ACEI) has been reported to dramatically improve outcome, with a fall of the 12-month mortality from 76% to less than 15% in the United-States. Despite prognostic improvement, SRC remains a severe manifestation of SSc and functional outcome and survival remains poor. Bosentan is a specific, orally active, dual endothelin receptor antagonist that has recently been approved for the treatment of primary pulmonary arterial hypertension and for the prevention of ischemic digital ulcers. Bosentan could have therapeutic benefits on others vascular injuries and particularly in SRC.

Detailed Description
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Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive collagen deposition, autoimmunity and by vascular hyper-reactivity and obliterative microvascular phenomena that involves multiple organs. Scleroderma Renal Crisis (SRC) occurs in 5% of patients and mainly with diffuse cutaneous SSc. The routine use of angiotensin-converting enzyme inhibitors (ACEI) has been reported to dramatically improve outcome, with a fall of the 12-month mortality from 76% to less than 15% in the United-States. Despite prognostic improvement, SRC remains a severe manifestation of SSc and functional outcome and survival remains poor. Bosentan is a specific, orally active, dual endothelin receptor antagonist that has recently been approved for the treatment of primary pulmonary arterial hypertension and for the prevention of ischemic digital ulcers. Bosentan could have therapeutic benefits on others vascular injuries and particularly in SRC.

Official Title
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Effect of Bosentan in the Course of Scleroderma Renal Crisis

Conditions
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Scleroderma Renal Crisis

Intervention / Treatment
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* Drug: Bosentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥ 18 years Patients had to fulfil ACR and/or LEROY et MEDSGER criteria for systemic sclerosis Patients had to fulfil criteria for renal systemic sclerosis Written informed consent obtained Exclusion Criteria: Scleroderma renal crisis occuring before the age of eighteen Patients who are receiving bosentan within one month of inclusion for pulmonary arterial hypertension or digital ulcers prevention Other treatment by selective or nonselective antagonist endothelin receptor Left ventricle systolic dysfunction (EF < 40 %) Patients with systolic blood pressure < 85mm Hg Progressive cancer or considered cured for less than 5 years Patients with a known hypersensitivity to bosentan or any of the excipients Patients with HIV, HCV, HBV infection Patients with Liver disease Child-Pugh B and C Patients who are pregnant or breast-feeding Women of child-bearing age who are sexually active without practising reliable methods of contraception Patients who do not give informed consent

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: Bosentan<br>Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks | Drug: Bosentan<br>* Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the efficacy of bosentan (Tracleer) in patients with scleroderma renal crisis on renal function |  | 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of bosentan in patients with scleroderma renal crisis over 6 months of treatment |  | 6 months | 
| 1 year overall survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scleroderma renal crisis, angiotensin converting enzyme inhibitors, bosentan, endothelin receptor antagonist