Effect of Bosentan in Scleroderma Renal Crisis (ScS-REINBO)

Effect of Bosentan in the Course of Scleroderma Renal Crisis

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.

Study Overview

• Status: Completed
• Conditions: Scleroderma Renal Crisis
• Intervention / Treatment: Drug: Bosentan

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bosentan; Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks	Drug: Bosentan; Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Actelion
• Investigators: Principal Investigator: Alice BEREZNE, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: November 12, 2010
• First Submitted That Met QC Criteria: November 15, 2010
• First Posted (ESTIMATE): November 16, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 5, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: endothelin receptor antagonist; bosentan; angiotensin converting enzyme inhibitors; Scleroderma renal crisis
• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: P081217