Effect of Bosentan in the Course of

Scleroderma Renal Crisis

Patrocinador: Assistance Publique - H?pitaux de Paris
Colaboradores: Actelion
Informacin proporcionada por: Assistance Publique - H?pitaux de Paris
Identificador: NCT01241383
Propsito
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.
Tipo de
estudio:
Interventional
Diseo del
estudio:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention
Model: Single Group Assignment, Masking: Open Label, Primary Purpose:
Treatment
Recursos/enlaces proporcionados por NLM:
Matrcula estimada: 15
Estudiar la fecha de inicio: December 2010
Calcula la fecha de finalizacin de primaria: December 2011
Armas
Bosentan:Experimental
Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks
Intervenciones asignadas
Drug:Bosentan
Bosentan 62.5mg bid x 4 weeks; up-titrated to 125mg bid x 20 weeks
Elegibilidad
Edades elegibles para su estudio: 18 Years
Gneros elegible para estudio: Both
Acepta a voluntarios sanos: No
Criterios
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

Investigadores
Investigador: Alice BEREZNE, PhD - Principal Investigator - AP-HP