Scleroderma Renal Crisis
Conditions
Keywords
Scleroderma renal crisis, angiotensin converting enzyme inhibitors, bosentan, endothelin receptor antagonist
Brief summary
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
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.
Interventions
DRUGBosentan
Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks
Sponsors
Assistance Publique - Hôpitaux de Paris
Actelion
URC-CIC Paris Descartes Necker Cochin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To explore the efficacy of bosentan (Tracleer) in patients with scleroderma renal crisis on renal function | 6 and 12 months |
Secondary
| Measure | 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 |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORAlice BEREZNE, PhD
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed