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Ulcerative ColitisPhase 4CYSIFNCT00542152

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

A Phase 4 study testing CYCLOSPORINE VS INFLIXIMAB in people with Ulcerative Colitis and Steroid Refractory, run by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives at 41 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ulcerative Colitis, Steroid Refractory
What is being tested?
CYCLOSPORINE VS INFLIXIMAB
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
41 sitesin 5 countries
Study dates
Jun 2007to Oct 2010
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 20Show fewer
  • 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.

Trial locations and contacts

41 sites in 5 countries.

41 sites in 5 countries

France31 sites

  • Chu Amiens

    Amiens, 80054

  • Ch Avignon

    Avignon, 84000

  • Chu Besancon

    Besançon, 25030

  • CHU CAEN

    Caen, 14033

  • Chu Clermont-Ferrand

    Clermont-Ferrand, 63003

  • Hopital Beaujon

    Clichy, 92110

  • Hopital Louis Mourrier

    Colombes, 92700

  • Hopital Henri Mondor

    Créteil, 94010

  • Hopital Bicetre

    Le Kremlin-Bicêtre, 94275

  • Chru Lille

    Lille, 59037

  • Chu Marseille - Hopital Nord

    Marseille, 13915

  • Ch Le Raincy Montfermeil

    Montfermeil, 93370

  • Chu Nantes

    Nantes, 44093

  • CHU NICE

    Nice, 06202

  • Hopital Lariboisiere

    Paris, 75010

  • Hopital Saint Louis

    Paris, 75010

  • Hopital St Antoine

    Paris, 75012

  • Hopital Cochin

    Paris, 75014

  • Hopital Georges Pompidou

    Paris, 75015

  • Hopital Bichat

    Paris, 75018

  • Institut Mutualiste Montsouris (Imm)

    Paris, 75674

  • Hopital Haut Leveque

    Pessac, 33604

  • CHU LYON

    Pierre-Bénite, 69495

  • Chu Reims

    Reims

  • Chu Rennes

    Rennes, 35033

  • Chu Rouen

    Rouen, 76031

  • Chu Saint Etienne

    Saint-Etienne, 42270

  • Chu Strasbourg

    Strasbourg, 67091

  • Chu Toulouse

    Toulouse, 31403

  • Chu Tours

    Tours, 37044

  • Chu Nancy

    Vandœuvre-lès-Nancy, 54500

Other trials in France

Belgium4 sites

  • Hopital Erasme

    Brussels, 1070

  • Ulb - Clinique Saint Luc

    Brussels, 1200

  • Gent University Hospital

    Ghent, 9000

  • Leuven University Hospital

    Leuven, 3000

Other trials in Belgium

Spain4 sites

  • Hospital Clinic

    Barcelona, 08036

  • Hospital Mutua de Terressa

    Barcelona, 08221

  • Hospital de la Princesa

    Madrid, 28006

  • Hospital Ramon Y Cajal

    Madrid, 28034

Other trials in Spain

Finland1 site

  • Helsinki University Hospital

    Helsinki, 00029

Other trials in Finland

Italy1 site

  • Istituto Clinico Humanitas

    Milan, 20089

Other trials in Italy

About this study

Official title: 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.

Read more

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

Being tested
CYCLOSPORINE VS INFLIXIMAB
Keywords
IBD, Ulcerative colitis, refractory to steroids
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CYCLOSPORINE VS INFLIXIMABDrug

    Also called Cyclosporine (IV)= Brand Name = Sandinuum, Cyclosporine (PO)= brand name = Neoral, Infliximab (IV)= brand name= Remicade

    • 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 groups in NCT00542152
Study groupRoleWhat they receive
CICLOActive comparatorCyclosporine 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.
Receives: Drug: CYCLOSPORINE VS INFLIXIMAB
INFLIXIMABActive comparatorINFLIXIMAB (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.
Receives: Drug: CYCLOSPORINE VS INFLIXIMAB

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. % 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

    Measured: Day 7

Secondary outcomes (1)

  1. % 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

    Measured: D98

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionJun 2007
  4. Study completionOct 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
115 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00542152
Sponsor's protocol ID
GETAID 2006-3
Acronym
CYSIF
Status last verified
Aug 2011
First submitted
8 Oct 2007
Last updated
31 Aug 2011
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 14084741

  • 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.

    PubMed 82099

  • 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.

    PubMed 11313301

  • 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.

    PubMed 8196726

  • 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.

    PubMed 14517785

  • 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.

    PubMed 15168804

  • 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.

    PubMed 11552900

  • 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.

    PubMed 10364029

  • 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.

    PubMed 15972298

  • 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;2005(1):CD004277. doi: 10.1002/14651858.CD004277.pub2.

    PubMed 15674937

  • 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.

    PubMed 15940615

  • 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.

    PubMed 12385442

  • 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.

    PubMed 12869077

  • 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.

    PubMed 15638237

  • 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.

    PubMed 15735427

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing CYCLOSPORINE VS INFLIXIMAB in people with Ulcerative Colitis and Steroid Refractory, run by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives at 41 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in France, Belgium, Spain, Finland, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

% 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00542152, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2011.

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