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

Phase 4

Completed

• Conditions: Ulcerative Colitis; Steroid Refractory
• Interventions: Drug: CYCLOSPORINE VS INFLIXIMAB

• Registration Number: NCT00542152
• Lead Sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Brief 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

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06
• Primary Completion: 2007-06
• Study First Submitted: 2007-10-08
• Study First Submitted QC: 2007-10-09
• Study First Posted: 2007-10-10
• Study Completion: 2010-10
• Status Verified: 2011-08
• Last Update Submitted: 2011-08-30
• Last Update Posted: 2011-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 115

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CICLO	CYCLOSPORINE VS INFLIXIMAB	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.
INFLIXIMAB	CYCLOSPORINE VS INFLIXIMAB	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.

Primary Outcome Measures

Name	Time	Method
% of patients with treatment failure defined as: absence of clinical response at D7 or absence of remission without steroids at D98 or relapse or severe adverse event leading to treatment interruption or colectomy or fatality between D0 and D98	Day 7

Secondary Outcome Measures

Name	Time	Method
% of patients in clinical response % patients in remission Lichtiger Index score MDAI score Time to discharge Endoscopic response colectomy rate Steroid dosage. Number of adverse events CMV infection	D98

Trial Locations

Locations (41)

Hopital Bicetre; 🇫🇷 Le Kremlin Bicetre, France

Chu Besancon; 🇫🇷 Besancon, France

Hopital Beaujon; 🇫🇷 Clichy, France

Hopital Georges Pompidou; 🇫🇷 Paris, France

Ch Avignon; 🇫🇷 Avignon, France

CHU CAEN; 🇫🇷 Caen, France

Hospital Ramon Y Cajal; 🇪🇸 Madrid, Spain

Istituto Clinico Humanitas; 🇮🇹 Milano, Italy

Hopital St Antoine; 🇫🇷 Paris, France

Hospital Clinic; 🇪🇸 Barcelona, Spain

Hospital de la Princesa; 🇪🇸 Madrid, Spain

Hospital Mutua de Terressa; 🇪🇸 Barcelona, Spain

Chu Clermont-Ferrand; 🇫🇷 Clermont-ferrand, France

Hopital Louis Mourrier; 🇫🇷 Colombes, France

Hopital Henri Mondor; 🇫🇷 Creteil, France

Chru Lille; 🇫🇷 Lille, France

Ch Le Raincy Montfermeil; 🇫🇷 Montfermeil, France

Chu Nantes; 🇫🇷 Nantes, France

CHU NICE; 🇫🇷 Nice, France

Hopital Saint Louis; 🇫🇷 Paris, France

Hopital Cochin; 🇫🇷 Paris, France

Hopital Bichat; 🇫🇷 Paris, France

Hopital Haut Leveque; 🇫🇷 Pessac, France

CHU LYON; 🇫🇷 Pierre Benite, France

Institut Mutualiste Montsouris (Imm); 🇫🇷 Paris, France

Chu Reims; 🇫🇷 Reims, France

Chu Rennes; 🇫🇷 Rennes, France

Chu Rouen; 🇫🇷 Rouen, France

Chu Saint Etienne; 🇫🇷 St Etienne, France

Chu Strasbourg; 🇫🇷 Strasbourg, France

Chu Tours; 🇫🇷 Tours, France

Chu Toulouse; 🇫🇷 Toulouse, France

Chu Nancy; 🇫🇷 Vandoeuvre Les Nancy, France

Leuven University Hospital; 🇧🇪 Leuven, Belgium

Chu Marseille - Hopital Nord; 🇫🇷 Marseille, France

Chu Amiens; 🇫🇷 Amiens, France

Hopital Lariboisiere; 🇫🇷 Paris, France

Gent University Hospital; 🇧🇪 Gent, Belgium

Ulb - Clinique Saint Luc; 🇧🇪 Bruxelles, Belgium

Hopital Erasme; 🇧🇪 Bruxelles, Belgium

Helsinki University Hospital; 🇫🇮 Helsinki, Finland