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

Sponsor

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives (Other)

Overall Status

Completed

CT.gov ID

NCT00542152

Collaborator

(none)

115

Enrollment

Locations

Arms

Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis Steroid Refractory	Drug: CYCLOSPORINE VS INFLIXIMAB	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

115 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Multicenter Open Label Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Jun 1, 2007

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CICLO 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.	Drug: CYCLOSPORINE 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 Other Names: Cyclosporine (IV)= Brand Name = Sandinuum Cyclosporine (PO)= brand name = Neoral Infliximab (IV)= brand name= Remicade
Active Comparator: 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.	Drug: CYCLOSPORINE 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 Other Names: Cyclosporine (IV)= Brand Name = Sandinuum Cyclosporine (PO)= brand name = Neoral Infliximab (IV)= brand name= Remicade

Arm

Intervention/Treatment

Active Comparator: CICLO

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.

Drug: CYCLOSPORINE 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

Other Names:

Cyclosporine (IV)= Brand Name = Sandinuum

Cyclosporine (PO)= brand name = Neoral

Infliximab (IV)= brand name= Remicade

Active Comparator: 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.

Drug: CYCLOSPORINE 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

Other Names:

Cyclosporine (IV)= Brand Name = Sandinuum

Cyclosporine (PO)= brand name = Neoral

Infliximab (IV)= brand name= Remicade

Outcome Measures

Primary Outcome Measures

% 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

% 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Erasme	Bruxelles	Belgium	1070
2	Ulb - Clinique Saint Luc	Bruxelles	Belgium	1200
3	Gent University Hospital	Gent	Belgium	9000
4	Leuven University Hospital	Leuven	Belgium	3000
5	Helsinki University Hospital	Helsinki	Finland	00029
6	Chu Amiens	Amiens	France	80054
7	Ch Avignon	Avignon	France	84000
8	Chu Besancon	Besancon	France	25030
9	CHU CAEN	Caen	France	14033
10	Chu Clermont-Ferrand	Clermont-ferrand	France	63003
11	Hopital Beaujon	Clichy	France	92110
12	Hopital Louis Mourrier	Colombes	France	92700
13	Hopital Henri Mondor	Creteil	France	94010
14	Hopital Bicetre	Le Kremlin Bicetre	France	94275
15	Chru Lille	Lille	France	59037
16	Chu Marseille - Hopital Nord	Marseille	France	13915
17	Ch Le Raincy Montfermeil	Montfermeil	France	93370
18	Chu Nantes	Nantes	France	44093
19	CHU NICE	Nice	France	06202
20	Hopital Lariboisiere	Paris	France	75010
21	Hopital Saint Louis	Paris	France	75010
22	Hopital St Antoine	Paris	France	75012
23	Hopital Cochin	Paris	France	75014
24	Hopital Georges Pompidou	Paris	France	75015
25	Hopital Bichat	Paris	France	75018
26	Institut Mutualiste Montsouris (Imm)	Paris	France	75674
27	Hopital Haut Leveque	Pessac	France	33604
28	CHU LYON	Pierre Benite	France	69495
29	Chu Reims	Reims	France
30	Chu Rennes	Rennes	France	35033
31	Chu Rouen	Rouen	France	76031
32	Chu Saint Etienne	St Etienne	France	42270
33	Chu Strasbourg	Strasbourg	France	67091
34	Chu Toulouse	Toulouse	France	31403
35	Chu Tours	Tours	France	37044
36	Chu Nancy	Vandoeuvre Les Nancy	France	54500
37	Istituto Clinico Humanitas	Milano	Italy	20089
38	Hospital Clinic	Barcelona	Spain	08036
39	Hospital Mutua de Terressa	Barcelona	Spain	08221
40	Hospital de la Princesa	Madrid	Spain	28006
41	Hospital Ramon Y Cajal	Madrid	Spain	28034