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

• Status: Completed
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Treatments: Cyclosporine; Cyclosporins; Infliximab

Criteria

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.