A proSpective Randomized Controlled Trial comParing infli... | NCT02177071

NCT02177071

Status Module

Name	Class
Saint-Louis Hospital, Paris, France	OTHER

Oversight Module

Description Module

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 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

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
INFLIXIMAB AND ANTI METABOLITE	No Intervention	continuing scheduled infliximab treatment and anti-metabolite
STOP INFLIXIMAB CONTINUING ANTI METABOLITE	Other	discontinuing infliximab and continuing the anti-metabolite	Drug: INFLIXIMAB
CONTINUING INFLIXIMAB AND discontinuing anti-metabolites	Other	CONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE	Drug: AZATHIOPRINE Drug: MERCAPTOPURINE Drug: Methotrexate

Name	Type	Description	Arm Group Labels	Other Names
INFLIXIMAB	Drug		STOP INFLIXIMAB CONTINUING ANTI METABOLITE
AZATHIOPRINE

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
co-primary efficacy end points	There will be two co-primary efficacy end points Relapse rate at 2 years, relapse being defined by either one of the following events: A CDAI>250 at any visit or between 150 and 250 with an increase of at least 70 points, over two consecutive visits one week apart associated with a CRP > 5 mg/l or a fecal calprotectin > 250 microg/g A new opening fistula, perianal or entero-cutaneous. An intra-abdominal abcess (size of at least 3 cm) or perianal abcess (size of at least 2 cm) An episode of intestinal obstruction due to Crohn's lesions confirmed by medical imaging and requiring hospitalisation (also considered as treatment failure, see below) Mean restricted time spent in remission This time will be computed in all patients, from baseline (CDAI <150 and with absence of fistula drainage) until relapse, as defined above, within the 2 first years. First and subsequent remissions will be summed up within the two first years.	2 ans

Secondary Outcomes

Measure	Description	Time Frame
relapse in each arm.	Time to relapse in each arm. Factors associated with time to relapse. Time to relapse according to CRP and calprotectin value measured every 2 months over the follow up.	2 years
Sustained clinical remission

Measure	Description	Time Frame
disability index	disability index	2 YEARS
adverse events and SAE	adverse events and SAE, events related to re-infusions,	2 YEARS

Eligibility Module

Name	Affiliation	Role
David Laharie	Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
St Vincent Hospital		Melbourne			Australia
CHU LIEGE - Sart Tilman

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39134391	Derived	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.
36640794

Ancestor Terms

ID	Term
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D013872	Thionucleosides
D013457	Sulfur Compounds
D009930	Organic Chemicals
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D013438	Sulfhydryl Compounds
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines

ID	Term
D015212	Inflammatory Bowel Diseases
D005759	Gastroenteritis
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D007410	Intestinal Diseases

ID	Term
D000069285	Infliximab
D001379	Azathioprine
D015122	Mercaptopurine
D008727	Methotrexate