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

August 30, 2011 updated by: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

115

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruxelles, Belgium, 1070
        • Hopital Erasme
      • Bruxelles, Belgium, 1200
        • Ulb - Clinique Saint Luc
      • Gent, Belgium, 9000
        • Gent University Hospital
      • Leuven, Belgium, 3000
        • Leuven University Hospital
  • Finland
      • Helsinki, Finland, 00029
        • Helsinki University Hospital
  • France
      • Amiens, France, 80054
        • CHU Amiens
      • Avignon, France, 84000
        • Ch Avignon
      • Besancon, France, 25030
        • CHU Besançon
      • Caen, France, 14033
        • CHU Caen
      • Clermont-ferrand, France, 63003
        • CHU Clermont-Ferrand
      • Clichy, France, 92110
        • Hopital Beaujon
      • Colombes, France, 92700
        • Hopital Louis Mourrier
      • Creteil, France, 94010
        • Hopital Henri Mondor
      • Le Kremlin Bicetre, France, 94275
        • Hôpital Bicêtre
      • Lille, France, 59037
        • CHRU Lille
      • Marseille, France, 13915
        • CHU Marseille - Hopital Nord
      • Montfermeil, France, 93370
        • Ch Le Raincy Montfermeil
      • Nantes, France, 44093
        • CHU Nantes
      • Nice, France, 06202
        • CHU Nice
      • Paris, France, 75010
        • Hôpital Saint Louis
      • Paris, France, 75010
        • Hopital Lariboisiere
      • Paris, France, 75014
        • Hopital Cochin
      • Paris, France, 75012
        • Hopital St Antoine
      • Paris, France, 75015
        • Hopital Georges Pompidou
      • Paris, France, 75674
        • Institut Mutualiste Montsouris (IMM)
      • Paris, France, 75018
        • Hôpital Bichat
      • Pessac, France, 33604
        • Hôpital Haut Lévêque
      • Pierre Benite, France, 69495
        • CHU Lyon
      • Reims, France
        • CHU Reims
      • Rennes, France, 35033
        • CHU Rennes
      • Rouen, France, 76031
        • CHU Rouen
      • St Etienne, France, 42270
        • CHU Saint Etienne
      • Strasbourg, France, 67091
        • CHU Strasbourg
      • Toulouse, France, 31403
        • CHU Toulouse
      • Tours, France, 37044
        • Chu Tours
      • Vandoeuvre Les Nancy, France, 54500
        • CHU Nancy
  • Italy
      • Milano, Italy, 20089
        • Istituto Clinico Humanitas
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clínic
      • Barcelona, Spain, 08221
        • Hospital Mutua de Terressa
      • Madrid, Spain, 28034
        • Hospital Ramón y Cajal
      • Madrid, Spain, 28006
        • Hospital de La Princesa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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
Time Frame: Day 7
Day 7

Secondary Outcome Measures

Outcome 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
Time Frame: D98
D98

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Investigators

  • Principal Investigator: David LAHARIE, MD, Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

October 8, 2007

First Submitted That Met QC Criteria

October 9, 2007

First Posted (Estimate)

October 10, 2007

Study Record Updates

Last Update Posted (Estimate)

August 31, 2011

Last Update Submitted That Met QC Criteria

August 30, 2011

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GETAID 2006-3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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