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

Conditions

Steroid Refractory, Ulcerative Colitis

Keywords

IBD, Ulcerative colitis, refractory to steroids

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

David Laharie, Arnaud Bourreille, Julien Branche, Matthieu Allez, Yoram Bouhnik et al. (30 authors)

Gut2017-01-04150 citations

10.1136/gutjnl-2016-313060

Ciclosporine versus Infliximab dans la colite aiguë grave résistante à la corticothérapie intra-veineuse : étude randomisée contrôlée en parallèle

M. Simon

Côlon & Rectum2016-01-29

10.1007/s11725-016-0630-x

Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.

Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Nachury M, Moreau J, Delchier JC, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Dupas JL, Carbonnel F, Bommelaer G, Coffin B, Roblin X, Van Assche G, Esteve M, Färkkilä M, Gisbert JP, Marteau P, Nahon S, de Vos M, Franchimont D, Mary JY, Colombel JF, Lémann M, Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.

2012-10-10440 citations

10.1016/s0140-6736(12)61084-8

Interventions

DRUGCYCLOSPORINE VS INFLIXIMAB

* Cyclosporine 2mg/kg/day intravenous for 7 days then Neoral 4mg/kg/day orally for 3 months. * Infliximab 5mg/kg at weeks 0, 2 and 6

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame
% 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

Measure	Time frame
% 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

Countries

Belgium, Finland, France, Italy, Spain

Outcome results

None listed