Stop Infliximab in Patients With Crohn's Disease

Crohn Disease Clinical Trial

— STORI  

Official title:

Prospective Study of Predictive Factors of Sustained Remission of Crohn's Disease After Stopping Infliximab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00571337
• Other study ID #: GETAID 2005-1
• Status: Completed
• Phase: Phase 3
• First received: July 25, 2007
• Last updated: July 22, 2010
• Start date: December 2005
• Est. completion date: July 2010

Study information

• Verified date: July 2010
• Source: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Infliximab
Stopping infliximab in patients having been treated with this drug for at least one year and in stable remission for at least 6 month.

Locations

Country	Name	City	State
Belgium	Gent University Hospital	Gent
Belgium	CHU LIEGE - Sart Tilman	Liege
France	Chu Amiens	Amiens
France	Chu Besancon	Besancon
France	Hopital Saint Andre	Bordeaux
France	CHU CAEN	Caen
France	Hopital Beaujon	Clichy
France	Hopital Louis Mourier	Colombes
France	Hopital Henri Mondor	Creteil
France	CHRU Lille	Lille
France	Chu Marseille - Hopital Nord	Marseille
France	Ch Le Raincy Montfermeil	Montfermeil
France	Chu Montpellier	Montpellier
France	Chu Nantes	Nantes
France	Hopital Georges Pompidou	Paris
France	Hopital Lariboisiere	Paris
France	Hopital Saint Louis	Paris
France	Hopital Haut Leveque	Pessac
France	CHU LYON	Pierre Benite
France	Chu Rouen	Rouen
France	Chu Strasbourg	Strasbourg
France	Chu Toulouse	Toulouse
France	Chu Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Countries where clinical trial is conducted

Belgium,  France, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Tampo Y, Yonaha M. Antioxidant mechanism of Mn(II) in phospholipid peroxidation. Free Radic Biol Med. 1992;13(2):115-20. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Time to relapse over one year	No
Primary	Evaluation of demographic, clinical and endoscopic factors predictive of relapse of Crohn's disease after stopping infliximab, with univariate and multivariate analysis.		Factors influencing time to relapse over one year.	No
Secondary	Tolerance and safety of infliximab retreatment in patients experiencing a relapse.		Follow up over 4 months including 3 infliximab retreatment s.	Yes
Secondary	predictive factors of short term-relapse (<2 months) after stopping infliximab, in the follow up of the patients.		at least 12 month and a maximum of 18 months.	No
Secondary	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.		4 weeks	No