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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
Actelion
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01241383
First received: November 12, 2010
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Scleroderma Renal Crisis
Drug: Bosentan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Bosentan in the Course of Scleroderma Renal Crisis

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • To explore the efficacy of bosentan (Tracleer) in patients with scleroderma renal crisis on renal function [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of bosentan in patients with scleroderma renal crisis over 6 months of treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • 1 year overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: December 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241383

Contacts
Contact: Alice BEREZNE, PhD +33 (0)1 58 41 29 70 alice.berezne@cch.aphp.fr
Contact: Laurence LECOMTE, PhD ++33171196494 laurence.lecomte@nck.aphp.fr

Locations
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 Recruiting
Paris, France, 75014
Contact: Alice Bérezné, PhD    +33 (0)1 58 41 29 70    alice.berezne@cch.aphp.fr   
Principal Investigator: Alice BEREZNE, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Actelion
Investigators
Principal Investigator: Alice BEREZNE, PhD AP-HP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01241383     History of Changes
Other Study ID Numbers: P081217
Study First Received: November 12, 2010
Last Updated: April 11, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Scleroderma renal crisis
angiotensin converting enzyme inhibitors
bosentan
endothelin receptor antagonist

Additional relevant MeSH terms:
Scleroderma, Localized
Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Skin Diseases
Angiotensin-Converting Enzyme Inhibitors
Bosentan
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 20, 2014