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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
ClinicalTrials.gov Identifier:
NCT00542152
First received: October 8, 2007
Last updated: August 30, 2011
Last verified: August 2011
  Purpose

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 Intervention Phase
Ulcerative Colitis
Steroid Refractory
Drug: CYCLOSPORINE VS INFLIXIMAB
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives:

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 [ Time Frame: Day 7 ] [ Designated as safety issue: No ]

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 [ Time Frame: D98 ] [ Designated as safety issue: No ]

Enrollment: 115
Study Start Date: June 2007
Study Completion Date: October 2010
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00542152

  Show 41 Study Locations
Sponsors and Collaborators
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Investigators
Principal Investigator: David LAHARIE, MD Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
ClinicalTrials.gov Identifier: NCT00542152     History of Changes
Other Study ID Numbers: GETAID 2006-3
Study First Received: October 8, 2007
Last Updated: August 30, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee

Keywords provided by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives:
IBD
Ulcerative colitis
refractory to steroids

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes
Cyclosporins
Cyclosporine
Infliximab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 26, 2014