Last updated on January 2019

A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy


Brief description of study

Phase IV

Design : Prospective, open-label, randomized three-arms study

Main Inclusion criteria Luminal Crohn's disease patients with steroid free remission for at least 6 months and a combination therapy with infliximab and anti-metabolites for at least 8 months

Primary objective To demonstrate that Infliximab scheduled maintenance with or without antimetabolites is superior to antimetabolites alone to maintain sustained steroid-free remission over 2 years, while the latter is non inferior with regards to the mean time spent in remission over the same duration

Main co-primary end points Clinical relapse rate at 2 years Mean remission duration within 2 years Study treatment Infliximab, Mercaptopurine, azathioprine, methotrexate.

Number of subjects 300 randomized patients (100 per arm)

Study duration: 2 + 2 years Enrollment: 2 years + 1 year Follow-up: 2 years

Detailed Study Description

3. STUDY OBJECTIVES 3.1. Primary objective To assess the effect of two withdrawal strategies over two years in patients with stable remission for more than 6 months on combination therapy with infliximab and antimetabolites, and demonstrate that continued combination of infliximab and antimetabolites or continued monotherapy with infliximab are both superior to antimetabolites alone for maintaining sustained steroid-free clinical remission, while antimetabolites alone are non-inferior with regards to the mean time spent in remission 3.2. Secondary objectives

  • To identify baseline predictive factors of relapse in the three study groups.
  • To assess the ability of blood CRP and fecal calprotectin to predict short term relapse in the three groups.
  • To assess time spent inclinical remission in the three groups.
  • To assess the rate of treatment failure in the three study groups.
  • To assess the time to treatment failure in the three study groups.
  • To assess progression of bowel damage in the three groups.
  • To assess the safety and efficacy of infliximab retreatment in the antimetabolites group.
  • To assess safety in the three study groups.
  • To assess the health related quality of life in the three study groups.
  • To assess direct and indirect costs in the three study groups.
  • To assess evolution of blood CRP and fecal calprotectin in the three study groups.
  • To assess evolution of infliximab trough levels and ATI in the two infliximab scheduled maintenance groups.
  • To assess genetic association with the various clinical and biological outcomes.
  • To assess the impact of 6TGN levels on the various clinical and biological outcomes in the purine treated patients 4. STUDY POPULATION 4.1. Selection of study population Patients to be included are those who have been in steroid free remission for at least 6 months and with scheduled infliximab/antimetabolites combination therapy for at least 8 months, with a scheduled infliximab treatment administrated every 8 weeks for the last 4 months.

4.2. Source of recruitment Patients are recruited from participating GETAID IBD-centers in France, Belgium and SOIBD IBD-centers in Sweden, and selected centres in UK, Germany, Netherland and Australia 4.3. Inclusion criteria

To be eligible all of the following criteria must be met:

  • Diagnosis of Crohn's disease.
  • Male or female, age > 18 years.
  • Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn's disease.
  • Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
  • Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 4 months.
  • Antimetabolites administered at a stable dosage for the last 3 months: at least 1 mg/Kg or 2 mg/Kg for mercaptopurine and azathioprine, respectively, or the highest tolerated dosage if intolerance to standard dose;(lower dose than standard dose is also allowed if 6 TGN > 235 pmol) ; at least 15 mg/week subcutaneously for methotrexate.
  • Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
  • CDAI < 150 at baseline.
  • A contraceptive during the whole study
  • Patients able to understand the information provided to them and to give written informed consent for the study

4.4. Exclusion criteria

  • Patients who have presented a severe acute or delayed reaction to infliximab.
  • Perianal fistulae as the main indication for infliximab treatment
  • Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
  • Patients with ostomy or ileoanal pouch
  • Pregnancy or planned pregnancy during the study
  • Inability to follow study procedures as judged by the investigator
  • Non-compliant subjects.
  • Participation in another therapeutic study

Clinical Study Identifier: NCT02177071

Find a site near you

Start Over

Chu Clermont-Ferrand

Clermont-ferrand, France
  Connect »

Chu Tours

Tours, France
  Connect »

Hopital Bicetre

Le Kremlin Bicetre, France
  Connect »

Chu Rouen

Rouen, France
  Connect »

Chu Toulouse

Toulouse, France
  Connect »

Chu Rennes

Rennes, France
  Connect »

Chu Nantes

Nantes, France
  Connect »

CHU LYON

Pierre Benite, France
  Connect »

Chu Amiens

Amiens, France
  Connect »

Chu Besancon

Besancon, France
  Connect »

Chu Kremlin Bicetre

Kremlin Bicetre, France
  Connect »

Chu Lille

Lille, France
  Connect »

Chu Montpellier

Montpellier, France
  Connect »

Chu Reims

Reims, France
  Connect »

Chu Strasbourg

Strasbourg, France
  Connect »

Ch Gustave Dron

Tourcoing, France
  Connect »

Chr Valencienne

Valencienne, France
  Connect »

Chu Nancy

Vandoeuvre Les Nancy, France
  Connect »