Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis
Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis
PHASE: IV

 TYPE OF STUDY: With direct benefit.

 DESCRIPTIVE: Multicenter, randomized, open label study.

 INCLUSION CRITERIA: Steroid-refractory ulcerative colitis.

 OBJECTIVES: To compare the efficacy of cyclosporine with infliximab in steroid- refractory
 attacks of ulcerative colitis.

 STUDY TREATMENTS:Cyclosporine 2mg/kg/day intravenous(IV)for 7days then Neoral 4mg/kg/day
 orally for 3 months. Infliximab 5mg/kg at Weeks 0, 2 and 6.

 NUMBER OF PATIENTS: 50 patients in each group i.e. a total of 100 patients.

 INCLUSION PERIOD: 24 months.

 STUDY DURATION: 27 months.

 MAIN EVALUATION CRITERIA:

 Clinical response at D7 according to the Lichtiger Index score AND Clinical Remission at D98
 according to the Mayo Disease Activity Index score

 SECONDARY EVALUATION CRITERIA:

 Clinical remission at D98 (according to the Mayo Disease Activity Index score) Endoscopic
 response Colectomy rate Tolerance
Inclusion Criteria:

 -  Age > 18 years.

 -  Diagnosis of UC according to Lennard-Jones criteria (Appendix 1).

 -  Endoscopically demonstrated colorectal lesions localized above the anal margin and
 extending at least up to 15cm proximally.

 -  Severe acute flare of UC with a Lichtiger Index score > 10.

 -  Refractoriness to high dose intravenous steroid therapy (≥ 0.8 mg/kg/d of
 methylprednisolone or equivalent) given for at least 5 days.

 -  Adequate contraception for male or female subjects of childbearing potential, which
 will be continued throughout the study and at least 3 months after study termination.

 Exclusion Criteria:

 -  Pregnant or breast-feeding woman.

 -  Previous treatment with cyclosporine or infliximab.

 -  Azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before
 inclusion.

 -  Indication for immediate surgery.

 -  History of colorectal dysplasia.

 -  Diagnosis of Crohn's disease.

 -  Positive stool tests for amoebiasis and/or positive bacteriological culture for
 Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium
 difficile B toxin in the stools.

 -  Renal failure (creatininemia > upper limit of normal laboratory value).

 -  Uncontrolled high blood pressure.

 -  HIV, HBV viral infection (except the presence of positive anti-HBs antibodies) with
 serology not older than 3 months.

 -  Uncontrolled bacterial or active viral infection.

 -  Past medical history of malignant condition in the last 5 years (including leukaemia,
 lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers.

 -  Past medical history of myocardial infarction or heart failure.

 -  Intradermal reaction to Tuberculin (Tubertest® 5 units) > 5mm.

 -  Active tuberculosis

 -  Untreated latent tuberculosis (see national recommendations. Appendix 2).

 -  Abnormal blood count with polynuclear neutrophils < 1,500 G/L or white cells < 3,000,
 or platelets < 100,000 G/L.

 -  Unexplained rise higher than 3 times the normal level for transaminases, alkaline
 phosphatases and/or higher than twice the normal level for bilirubin.

 -  Non-compliant subjects.

 -  Participation in another therapeutic study.