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

NCT ID: NCT02177071

Last Updated: 2022-08-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

211 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-09

Study Completion Date

2021-10-31

Brief Summary

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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 225 randomized patients (75 per arm)

Study duration: 3 + 2 years Enrollment: 3 years Follow-up: 2 years

Detailed Description

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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

Conditions

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Crohn's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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INFLIXIMAB AND ANTI METABOLITE

continuing scheduled infliximab treatment and anti-metabolite

Group Type NO_INTERVENTION

No interventions assigned to this group

STOP INFLIXIMAB CONTINUING ANTI METABOLITE

discontinuing infliximab and continuing the anti-metabolite

Group Type OTHER

INFLIXIMAB

Intervention Type DRUG

CONTINUING INFLIXIMAB AND discontinuing anti-metabolites

CONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE

Group Type OTHER

AZATHIOPRINE

Intervention Type DRUG

MERCAPTOPURINE

Intervention Type DRUG

Methotrexate

Intervention Type DRUG

Interventions

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INFLIXIMAB

Intervention Type DRUG

AZATHIOPRINE

Intervention Type DRUG

MERCAPTOPURINE

Intervention Type DRUG

Methotrexate

Intervention Type DRUG

Eligibility Criteria

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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 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; 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 for childbearing potential female patients.
* 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
* Steroid use ≤6 months prior to screening
* Currently receiving steroids, immunosuppressive agents (other than purine, methotrexate), biologic treatment (other than infliximab) or thalidomide
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Saint-Louis Hospital, Paris, France

OTHER

Sponsor Role collaborator

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Laharie

Role: PRINCIPAL_INVESTIGATOR

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Locations

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St Vincent Hospital

Melbourne, , Australia

Site Status

CHU LIEGE - Sart Tilman

Liège, Province De Liège, Belgium

Site Status

Gent University Hospital

Ghent, , Belgium

Site Status

Chu Clermont-Ferrand

Clermont-Ferrand, Auvergne-Rhône-Alpes, France

Site Status

CHU LYON

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Site Status

Chu Saint Etienne

Saint-Etienne, Auvergne-Rhône-Alpes, France

Site Status

Chu Besancon

Besançon, Bourgogne-Franche-Comté, France

Site Status

Chu Rennes

Rennes, Brittany Region, France

Site Status

Chu Tours

Tours, Centre-Val de Loire, France

Site Status

Chu Reims

Reims, Grand Est, France

Site Status

Chu Nancy

Vandœuvre-lès-Nancy, Grand Est, France

Site Status

Chu Amiens

Amiens, Hauts-de-France, France

Site Status

Chu Lille

Lille, Hauts-de-France, France

Site Status

Chr Valencienne

Valenciennes, Hauts-de-France, France

Site Status

Caen Unversity Hospital

Caen, Normandy, France

Site Status

CHU Bordeaux - Pessac

Pessac, Nouvelle-Aquitaine, France

Site Status

Chu Montpellier

Montpellier, Occitanie, France

Site Status

Chu Toulouse

Toulouse, Occitanie, France

Site Status

Chu Nantes

Nantes, Pays de la Loire Region, France

Site Status

CHU NICE

Nice, Provences Alpes Cote d'Azur, France

Site Status

Hopital Saint Joseph

Paris, , France

Site Status

Hopital Beaujon

Clichy, Île-de-France Region, France

Site Status

Chu Kremlin Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, France

Site Status

Hopital Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, France

Site Status

Hopital Saint Louis

Paris, Île-de-France Region, France

Site Status

Hopital St Antoine

Paris, Île-de-France Region, France

Site Status

Montsouris Mutualist Institute

Paris, Île-de-France Region, France

Site Status

Countries

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Australia Belgium France

References

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Pierre N, Huynh-Thu VA, Baiwir D, Mazzucchelli G, Fleron M, Trzpiot L, Eppe G, De Pauw E, Laharie D, Satsangi J, Bossuyt P, Vuitton L, Vieujean S, Colombel JF, Meuwis MA, Louis E; GETAID and the SPARE-Biocycle research group. External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab. Gut. 2024 Nov 11;73(12):1965-1973. doi: 10.1136/gutjnl-2024-332648.

Reference Type DERIVED
PMID: 39134391 (View on PubMed)

Louis E, Resche-Rigon M, Laharie D, Satsangi J, Ding N, Siegmund B, D'Haens G, Picon L, Bossuyt P, Vuitton L, Irving P, Viennot S, Lamb CA, Pollok R, Baert F, Nachury M, Fumery M, Gilletta C, Almer S, Ben-Horin S, Bouhnik Y, Colombel JF, Hertervig E; GETAID and the SPARE-Biocycle research group. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Mar;8(3):215-227. doi: 10.1016/S2468-1253(22)00385-5. Epub 2023 Jan 11.

Reference Type DERIVED
PMID: 36640794 (View on PubMed)

Hirten RP, Lakatos PL, Halfvarson J, Colombel JF. Reply. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1301-1302. doi: 10.1016/j.cgh.2020.07.061. Epub 2020 Nov 26. No abstract available.

Reference Type DERIVED
PMID: 33248096 (View on PubMed)

Other Identifiers

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GETAID 2014-03

Identifier Type: -

Identifier Source: org_study_id

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