Effect of Bosentan in Scleroderma Renal Crisis

Scleroderma Renal Crisis Clinical Trial

— ScS-REINBO  

Official title:

Effect of Bosentan in the Course of Scleroderma Renal Crisis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01241383
• Other study ID #: P081217
• Status: Completed
• Phase: Phase 2
• First received: November 12, 2010
• Last updated: July 5, 2016
• Start date: December 2010
• Est. completion date: June 2016

Study information

• Verified date: October 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma Renal Crisis
• Scleroderma, Diffuse
• Scleroderma, Localized
• Scleroderma, Systemic

Intervention

Drug:
• Bosentan
Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks

Locations

Country	Name	City	State
France	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	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Actelion

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To explore the efficacy of bosentan (Tracleer) in patients with scleroderma renal crisis on renal function		6 and 12 months	No
Secondary	To evaluate the safety and tolerability of bosentan in patients with scleroderma renal crisis over 6 months of treatment		6 months	Yes
Secondary	1 year overall survival		1 year	No