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
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's Disease
Intervention: INFLIXIMAB (Drug); AZATHIOPRINE (Drug); MERCAPTOPURINE (Drug); Methotrexate (Drug)
Phase: Phase 4
Status: Not yet recruiting
Sponsored by: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives Official(s) and/or principal investigator(s): Benjamin PARIENTE, doctor, Principal Investigator, Affiliation: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Overall contact: Edouard LOUIS, PHD, Phone: 0033142494988, Email: edouard.louis@ulg.ac.be
Summary
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 1
year
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 Follow-up: 2 years
Clinical Details
Official title: 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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: co-primary efficacy end points
Secondary outcome: relapse in each arm.Sustained clinical remission Treatment failure Tissue damage progression
Detailed 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 than6 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
1 year, with a scheduled infliximab treatment administrated every 8 weeks for the last
6 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 the USA.
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 12 months.
- Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 6 months.
- Antimetabolites administered at a stable dosage for the last 6 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 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
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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 12
months.
- Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 6 months.
- Antimetabolites administered at a stable dosage for the last 6 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 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
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
Locations and Contacts
Edouard LOUIS, PHD, Phone: 0033142494988, Email: edouard.louis@ulg.ac.be
Gent University Hospital, Gent 9000, Belgium
CHU LIEGE - Sart Tilman, Liege 4000, Belgium
Chu Amiens, Amiens 80054, France
Chu Besancon, Besancon 25030, France; Not yet recruiting LUCINE VUITON, MD LUCINE VUITON, MD, Principal Investigator
Caen Unversity Hospital, Caen 14033, France
Chu Clermont-Ferrand, Clermont-ferrand 63003, France
Hopital Beaujon, Clichy 92110, France
Hopital Louis Mourier, Colombes 92700, France
Hopital Henri Mondor, Creteil 94010, France
Chu Kremlin Bicetre, Kremlin Bicetre, France; Not yet recruiting FRANCK CARBONNEL, MD, Sub-Investigator
Hopital Bicetre, Le Kremlin Bicetre 94275, France
Chu Lille, Lille, France; Not yet recruiting Maria NACHURY, MD Maria NACHURY, MD, Principal Investigator
Chu Marseille - Hopital Nord, Marseille 13915, France
Ch Le Raincy Montfermeil, Montfermeil 93370, France
Chu Montpellier, Montpellier 34295, France; Not yet recruiting ROMAIN ALTWEGG, MD, Phone: +33467337394 ROMAIN ALTWEGG, MD, Sub-Investigator
Chu Nantes, Nantes 44093, France
CHU NICE, Nice 06202, France
Georges Pompidou European Hospital, Paris 75015, France
Hopital Bichat, Paris 75018, France
Hopital Cochin, Paris 75014, France
Hopital Lariboisiere, Paris 75010, France
Hopital Saint Louis, Paris 75010, France
Hopital St Antoine, Paris 75012, France
Montsouris Mutualist Institute, Paris 75674, France
CHU Bordeaux - Pessac, Pessac 33700, France
CHU LYON, Pierre Benite 69495, France
Chu Reims, Reims, France
Chu Rennes, Rennes 35033, France
Chu Rouen, Rouen 76031, France
Chu Saint Etienne, St Etienne 42270, France
Chu Strasbourg, Strasbourg 67091, France; Not yet recruiting Bernard DUCLOS, MD,PhD, Phone: +33388127442, Email: bduclos@noos.fr Bernard DUCLOS, MD,PhD, Principal Investigator JEAN MARIE REIMUND, MDPHD, Sub-Investigator
Chu Toulouse, Toulouse 31403, France
Ch Gustave Dron, Tourcoing 59208, France; Not yet recruiting GUENOLA VERNIER, MD GWENOLA VERNIER, MD, Principal Investigator
Chu Tours, Tours 37044, France
Chr Valencienne, Valencienne 59300, France; Not yet recruiting MEDINA BOUALIT, MD MEDINA BOUALIT, MD, Principal Investigator
Chu Nancy, Vandoeuvre Les Nancy 54500, France; Not yet recruiting LAURENT PEYRIN BIROULET, MD,PhD, Phone: +33383153354 Laurent PEYRIN-BIROULET, MD,PhD, Principal Investigator
Additional Information
Starting date: April 2015
Last updated: April 26, 2015
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