Clinical trial NCT01241383: Effect of Bosentan in Scleroderma Renal Crisis
Official title: Effect of Bosentan in the Course of Scleroderma Renal Crisis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Scleroderma Renal Crisis
Keywords: Scleroderma renal crisis
angiotensin converting enzyme inhibitors
bosentan
endothelin receptor antagonist
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Actelion
First posted: 2010-11-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To explore the efficacy of bosentan (Tracleer) in patients with scleroderma renal crisis on renal function
timeFrame: 6 and 12 months
Secondary outcomes:
measure: To evaluate the safety and tolerability of bosentan in patients with scleroderma renal crisis over 6 months of treatment
timeFrame: 6 months
measure: 1 year overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Pôle de médecine interne Centre de référence Maladies rares Groupe I Maladies systémiques et maladies auto-immunes rares en particulier Vascularites nécrosantes et les sclérodermies - Hôpital Cochin
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Alice BEREZNE, PhD
role: PRINCIPAL_INVESTIGATOR
References: