Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis
NCT ID: NCT00542152
Last Updated: 2011-08-31
Study Results
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Basic Information
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COMPLETED
PHASE4
115 participants
INTERVENTIONAL
2007-06-30
2010-10-31
Brief Summary
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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
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
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
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.
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
Interventions
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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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
ALL
No
Sponsors
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Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
OTHER
Responsible Party
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Principal Investigators
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David LAHARIE, MD
Role: PRINCIPAL_INVESTIGATOR
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Locations
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Hopital Erasme
Brussels, , Belgium
Ulb - Clinique Saint Luc
Brussels, , Belgium
Gent University Hospital
Ghent, , Belgium
Leuven University Hospital
Leuven, , Belgium
Helsinki University Hospital
Helsinki, , Finland
Chu Amiens
Amiens, , France
Ch Avignon
Avignon, , France
Chu Besancon
Besançon, , France
CHU CAEN
Caen, , France
Chu Clermont-Ferrand
Clermont-Ferrand, , France
Hopital Beaujon
Clichy, , France
Hopital Louis Mourrier
Colombes, , France
Hopital Henri Mondor
Créteil, , France
Hopital Bicetre
Le Kremlin-Bicêtre, , France
Chru Lille
Lille, , France
Chu Marseille - Hopital Nord
Marseille, , France
Ch Le Raincy Montfermeil
Montfermeil, , France
Chu Nantes
Nantes, , France
CHU NICE
Nice, , France
Hopital Lariboisiere
Paris, , France
Hopital Saint Louis
Paris, , France
Hopital St Antoine
Paris, , France
Hopital Cochin
Paris, , France
Hopital Georges Pompidou
Paris, , France
Hopital Bichat
Paris, , France
Institut Mutualiste Montsouris (Imm)
Paris, , France
Hopital Haut Leveque
Pessac, , France
CHU LYON
Pierre-Bénite, , France
Chu Reims
Reims, , France
Chu Rennes
Rennes, , France
Chu Rouen
Rouen, , France
Chu Saint Etienne
Saint-Etienne, , France
Chu Strasbourg
Strasbourg, , France
Chu Toulouse
Toulouse, , France
Chu Tours
Tours, , France
Chu Nancy
Vandœuvre-lès-Nancy, , France
Istituto Clinico Humanitas
Milan, , Italy
Hospital Clinic
Barcelona, , Spain
Hospital Mutua de Terressa
Barcelona, , Spain
Hospital de la Princesa
Madrid, , Spain
Hospital Ramon Y Cajal
Madrid, , Spain
Countries
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References
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Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994 Jun 30;330(26):1841-5. doi: 10.1056/NEJM199406303302601.
Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, Arts J, D'Hoore A, Penninckx F, Rutgeerts P. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003 Oct;125(4):1025-31. doi: 10.1016/s0016-5085(03)01214-9.
Arts J, D'Haens G, Zeegers M, Van Assche G, Hiele M, D'Hoore A, Penninckx F, Vermeire S, Rutgeerts P. Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis. Inflamm Bowel Dis. 2004 Mar;10(2):73-8. doi: 10.1097/00054725-200403000-00002.
Actis GC, Bresso F, Astegiano M, Demarchi B, Sapone N, Boscaglia C, Rizzetto M. Safety and efficacy of azathioprine in the maintenance of ciclosporin-induced remission of ulcerative colitis. Aliment Pharmacol Ther. 2001 Sep;15(9):1307-11. doi: 10.1046/j.1365-2036.2001.01019.x.
Cohen RD, Stein R, Hanauer SB. Intravenous cyclosporin in ulcerative colitis: a five-year experience. Am J Gastroenterol. 1999 Jun;94(6):1587-92. doi: 10.1111/j.1572-0241.1999.01149.x.
Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006 Jan;55(1):47-53. doi: 10.1136/gut.2005.068809. Epub 2005 Jun 21.
Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004277. doi: 10.1002/14651858.CD004277.pub2.
EDWARDS FC, TRUELOVE SC. THE COURSE AND PROGNOSIS OF ULCERATIVE COLITIS. Gut. 1963 Dec;4(4):299-315. doi: 10.1136/gut.4.4.299.
Truelove SC, Willoughby CP, Lee EG, Kettlewell MG. Further experience in the treatment of severe attacks of ulcerative colitis. Lancet. 1978 Nov 18;2(8099):1086-8. doi: 10.1016/s0140-6736(78)91816-0.
D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, Peeters M, Vermeire S, Penninckx F, Nevens F, Hiele M, Rutgeerts P. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001 May;120(6):1323-9. doi: 10.1053/gast.2001.23983.
Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005 Jun;128(7):1805-11. doi: 10.1053/j.gastro.2005.03.003.
Su C, Salzberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, Stein RB, Adler DR, Lichtenstein GR. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol. 2002 Oct;97(10):2577-84. doi: 10.1111/j.1572-0241.2002.06026.x.
Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Aliment Pharmacol Ther. 2003 Jul 15;18(2):175-81. doi: 10.1046/j.1365-2036.2003.01686.x.
Kohn A, Prantera C, Pera A, Cosintino R, Sostegni R, Daperno M. Infliximab in the treatment of severe ulcerative colitis: a follow-up study. Eur Rev Med Pharmacol Sci. 2004 Sep-Oct;8(5):235-7.
Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2005 Mar;11(3):213-8. doi: 10.1097/01.mib.0000160803.44449.a5.
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
Hasskamp J, Meinhardt C, Patton PH, Timmer A. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.
Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Vuitton L, Moreau J, Amiot A, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Fumery M, Carbonnel F, Bommelaer G, Coffin B, Roblin X, van Assche G, Esteve M, Farkkila M, Gisbert JP, Marteau P, Nahon S, de Vos M, Lambert J, Mary JY, Louis E; Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab. Gut. 2018 Feb;67(2):237-243. doi: 10.1136/gutjnl-2016-313060. Epub 2017 Jan 4.
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, Farkkila M, Gisbert JP, Marteau P, Nahon S, de Vos M, Franchimont D, Mary JY, Colombel JF, Lemann M; Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 2012 Dec 1;380(9857):1909-15. doi: 10.1016/S0140-6736(12)61084-8. Epub 2012 Oct 10.
Related Links
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Related Info
Other Identifiers
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GETAID 2006-3
Identifier Type: -
Identifier Source: org_study_id