Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
300

Inclusion Criterias

Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
CDAI < 150 at baseline.
...
Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
CDAI < 150 at baseline.
Diagnosis of Crohn's disease.
A contraceptive during the whole study for childbearing potential female patients.
Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn's disease.
Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 4 months.
Male or female, age > 18 years.
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; at least 15 mg/week subcutaneously for methotrexate.
Patients able to understand the information provided to them and to give written informed consent for the study

Exclusion Criterias

Steroid use ≤6 months prior to screening
Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
Patients who have presented a severe acute or delayed reaction to infliximab.
...
Steroid use ≤6 months prior to screening
Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
Patients who have presented a severe acute or delayed reaction to infliximab.
Patients with ostomy or ileoanal pouch
Non-compliant subjects.
Participation in another therapeutic study
Inability to follow study procedures as judged by the investigator
Pregnancy or planned pregnancy during the study
Currently receiving steroids, immunosuppressive agents (other than purine, methotrexate), biologic treatment (other than infliximab) or thalidomide
Perianal fistulae as the main indication for infliximab treatment

Summary

Conditions
Crohn's Disease
Type
Interventional
Phase
Phase 4
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 65 years
Gender
Both males and females

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 antimetabolite...

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

Inclusion Criterias

Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
CDAI < 150 at baseline.
...
Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
CDAI < 150 at baseline.
Diagnosis of Crohn's disease.
A contraceptive during the whole study for childbearing potential female patients.
Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn's disease.
Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 4 months.
Male or female, age > 18 years.
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; at least 15 mg/week subcutaneously for methotrexate.
Patients able to understand the information provided to them and to give written informed consent for the study

Exclusion Criterias

Steroid use ≤6 months prior to screening
Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
Patients who have presented a severe acute or delayed reaction to infliximab.
...
Steroid use ≤6 months prior to screening
Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
Patients who have presented a severe acute or delayed reaction to infliximab.
Patients with ostomy or ileoanal pouch
Non-compliant subjects.
Participation in another therapeutic study
Inability to follow study procedures as judged by the investigator
Pregnancy or planned pregnancy during the study
Currently receiving steroids, immunosuppressive agents (other than purine, methotrexate), biologic treatment (other than infliximab) or thalidomide
Perianal fistulae as the main indication for infliximab treatment

Locations

Paris, Ile De France, 75010
Clermont-ferrand, Auvergne Rhone Alpes, 63003
Paris, 75014
Amiens, Hauts De France, 80054
Gent, 9000
...
Paris, Ile De France, 75010
Clermont-ferrand, Auvergne Rhone Alpes, 63003
Paris, 75014
Amiens, Hauts De France, 80054
Gent, 9000
Nantes, Pays De La Loire, 44093
Lille, Hauts De France, 59000
St Etienne, Auvergne Rhone Alpes, 42270
Vandoeuvre Les Nancy, Grand Est, 54500
Montpellier, Occitanie, 34295
Besancon, Bourgogne-Franche-Comte, 25030
Pessac, Nouvelle-aquitaine, 33700
Nice, Provences Alpes Cote d'Azur, 06202
Rennes, Bretagne, 35033
Paris, Ile De France, 75674
Le Kremlin-Bicêtre, Ile De France, 94270
Paris, Ile De France, 75012
Le Kremlin Bicetre, Ile De France, 94275
Valenciennes, Hauts De France, 59300
Pierre Benite, Auvergne Rhone Alpes, 69495
Melbourne
Toulouse, Occitanie, 31403
Liege, Province De Liège, 4000
Clichy, Ile De France, 92110
Caen, Normandie, 14033
Tours, Centre Val De Loire, 37044
Reims, Grand Est, 51092

Tracking Information

NCT #
NCT02177071
Collaborators
Saint-Louis Hospital, Paris, France
Investigators
  • Principal Investigator: Benjamin PARIENTE, doctor Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
  • David Laharie Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives