Stop Infliximab in Patients With Crohn's Disease
Information source: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Crohn Disease
Intervention: Infliximab (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives Official(s) and/or principal investigator(s): Louis Edouard, PhD, Principal Investigator, Affiliation: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Summary
1 Project summary 1. 1 Rational. Accent 1 study has demonstrated the superiority of
Infliximab over placebo in a systematic treatment strategy of Crohn 's disease every 8 weeks
during one year. However the optimal strategy beyond one year of treatment is not
established. Particularly, the need for carrying on systematic treatment with infliximab in
all the patients has not been demonstrated.
1. 2 Primary objective. Determine factors associated with a low risk of clinical relapse
after stopping infliximab in CD patients in remission (CDAI<150) and regularly treated with
infliximab for at least one year.
1. 3 Main objective and main judgement criteria. Determine predictive factors for relapse
within one year after stopping infliximab. Main judgement criteria is the clinical relapse
after stopping infliximab. Clinical relapse is defined either by a CDAI>250 or by a CDAI
between 150 and 250 if this CDAI is confirmed over two consecutive weeks with an increase of
at least 70 points over baseline for the two consecutive measures.
1. 4 Secondary objectives and judgement criteria. Determine the time to-relapse Determine
predictive factors for short-term relapse (<2 months)after stopping infliximab.
Determine response to infliximab retreatment in these patients. Determine tolerance to
infliximab retreatment in these patients. Determine predictive factors for an absence of
response to retreatment. Determine predictive factors for infliximab retreatment
intolerance. Determine sustained response in the retreated patients.
1. 5 Type of study Open-label prospective study of stopping regular treatment. Inclusion
period: minimum one year, possibly prolonged to reach 100 patients. Patients will be
followed up every two months for at least 18 months after stopping infliximab.
1. 6 Justification of the number of patients Number of patients to include is at least 100.
This recruitment should be reached within one year. This number should allow to disclose
predictive factors associated with a relative risk of at least 2 if this factor is
equilibrated (50% at risk patients) or 3 is this factor is disequilibrated (90% at risk
patients).
Clinical Details
Official title: Prospective Study of Predictive Factors of Sustained Remission of Crohn's Disease After Stopping Infliximab
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Relapse of Crohn's disease assessed by a CDAI > 250 or a CDAI between 150 and 250 at two consecutive weeks, with an increase of at least 70 points over baseline.Evaluation of demographic, clinical and endoscopic factors predictive of relapse of Crohn's disease after stopping infliximab, with univariate and multivariate analysis.
Secondary outcome: Tolerance and safety of infliximab retreatment in patients experiencing a relapse.predictive factors of short term-relapse (<2 months) after stopping infliximab, in the follow up of the patients. Clinical response to infliximab retreatment, assessed 4 weeks after retreatment using CDAI. A clinical response is defined by a 70 points drop (and at least 25%) as compared to relapse CDAI.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion criteria:
- Crohn's disease.
- Age > 18 years.
- Patient written informed consent.
- Patient having been treated with infliximab for confirmed Crohn's disease with active
intestinal lesions.
- Patient treated with infliximab for at least 1 year, associated with an
immunosuppressor for at least one year, with a maximum interval between 2 infliximab
infusions of 3 months.
- Patient with continuous remission without steroids for at least 6 months, except IV
steroids for infusion reaction prophylaxis.
- CDAI<150.
- Contraception all over the study.
Exclusion criteria:
- Patient having experienced an severe acute infusion reaction to infliximab, defined
by an anaphylactoïd reaction (drop in blood pressure, bronchospasm, dyspnea)
requiring the arrest of the infliximab infusion.
- Patient having experienced a severe delayed infusion reaction to infliximab, defined
by fever, arthralgia, myalgia, requiring a steroid treatment.
- Patient with dominant perianal disease and absence of active intestinal disease at
the time of infliximab induction.
- Patient with active perianal disease at the time of inclusion.
- Patient with stoma.
- Patient with debilitating extra-intestinal manifestation at the time of inclusion.
- Non cooperating subjects.
- Pregnant or lactating women.
Locations and Contacts
Gent University Hospital, Gent 9000, Belgium
CHU LIEGE - Sart Tilman, Liege 4000, Belgium
Chu Amiens, Amiens 80054, France
Chu Besancon, Besancon 25030, France
Hopital Saint Andre, Bordeaux 33075, France
CHU CAEN, Caen 14033, France
Hopital Beaujon, Clichy 92110, France
Hopital Louis Mourier, Colombes 92700, France
Hopital Henri Mondor, Creteil 94010, France
CHRU Lille, Lille, France
Chu Marseille - Hopital Nord, Marseille 13915, France
Ch Le Raincy Montfermeil, Montfermeil 93370, France
Chu Montpellier, Montpellier 34295, France
Chu Nantes, Nantes 44093, France
Hopital Georges Pompidou, Paris 75015, France
Hopital Lariboisiere, Paris 75010, France
Hopital Saint Louis, Paris 75010, France
Hopital Haut Leveque, Pessac 33604, France
CHU LYON, Pierre Benite 69495, France
Chu Rouen, Rouen 76031, France
Chu Strasbourg, Strasbourg 67091, France
Chu Toulouse, Toulouse 31403, France
Chu Tours, Tours 37044, France
Additional Information
Related publications: Vermeire S, Louis E, Carbonez A, Van Assche G, Noman M, Belaiche J, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, D'Haens G, Rutgeerts P; Belgian Group of Infliximab Expanded Access Program in Crohn's Disease. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn's disease. Am J Gastroenterol. 2002 Sep;97(9):2357-63. Parsi MA, Achkar JP, Richardson S, Katz J, Hammel JP, Lashner BA, Brzezinski A. Predictors of response to infliximab in patients with Crohn's disease. Gastroenterology. 2002 Sep;123(3):707-13. Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology. 2003 Apr;124(4):917-24. Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. Tampo Y, Yonaha M. Antioxidant mechanism of Mn(II) in phospholipid peroxidation. Free Radic Biol Med. 1992;13(2):115-20. Parsi MA, Lashner BA. Safety of infliximab: primum non nocere. The safety profile of infliximab in patients with Crohn's disease: the Mayo Clinic experience in 500 patients. Inflamm Bowel Dis. 2004 Jul;10(4):486-7. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001 Oct 11;345(15):1098-104.
Starting date: December 2005
Last updated: July 22, 2010
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