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

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Status and phase: Completed; Phase 4

Conditions: Steroid Refractory; Ulcerative Colitis

Treatments: Drug: CYCLOSPORINE VS INFLIXIMAB

Study type: Interventional

Funder types: Other

Identifiers

NCT00542152

GETAID 2006-3

Details and patient eligibility

About

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

Enrollment: 115 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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115 participants in 2 patient groups

CICLO

Active Comparator group

Description:

Cyclosporine will be administered by continuous intravenous infusion at the initial dose regimen of 2mg/kg per day. After 24 hours of treatment, cyclosporine trough level will be measured and the dose adapted in order to obtain a cyclosporinaemia level between 150 and 250 ng/ml. Cyclosporinaemia will be reassessed every 48 hours for the duration of the continuous intravenous treatment.

Treatment:

Drug: CYCLOSPORINE VS INFLIXIMAB

INFLIXIMAB

Active Comparator group

Description:

INFLIXIMAB (REMICADE) Infliximab in the form of a freeze-dried compound is conditioned in 100mg vials. Treatment will first be reconstituted in 250ml isotonic saline solution, and slowly infused at the dose of 5mg/kg in 2 hours. In patients with clinical response at D7 (Lichtiger Index score \< 10 for 2 consecutive days), two additional infliximab infusions will be administered at the dose of 5mg/kg at D14 and D42.

Treatment:

Drug: CYCLOSPORINE VS INFLIXIMAB