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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 11 June 2018
Main ID:  EUCTR2014-002311-41-NL
Date of registration: 18/12/2017
Prospective Registration: Yes
Primary sponsor: GETAID
Public 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. SPARE
Scientific 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. - GETAID 2014-3 SPARE
Date of first enrolment: 25/05/2018
Target sample size: 300
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002311-41
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
Number of treatment arms in the trial: 3
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes
Countries of recruitment
Belgium France Germany Netherlands Sweden United Kingdom
Contacts
Name: BRILLAULT GAELLE   
Address:  Hopital LARIBOISIERE Sce de Gastro enterologie 1 av Claude Vellefaux 75010 PARIS France
Telephone: 33617044633
Email: projet@getaid.org
Affiliation:  GETAID
Name: BRILLAULT GAELLE   
Address:  Hopital LARIBOISIERE Sce de Gastro enterologie 1 av Claude Vellefaux 75010 PARIS France
Telephone: 33617044633
Email: projet@getaid.org
Affiliation:  GETAID
Key inclusion & exclusion 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 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 for childbearing potential female patients.
• Patients able to understand the information provided to them and to give written informed consent for the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
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
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
Intervention(s)

Trade Name: REMICADE
Product Name: INFLIXIMAB
Pharmaceutical Form: Infusion

Trade Name: IMUREL
Product Name: azathioprine
Pharmaceutical Form: Tablet

Trade Name: METHOTREXATE
Product Name: METHOTREXATE
Pharmaceutical Form: Concentrate for cutaneous solution

Trade Name: PURINETHOL
Product Name: MERCAPTOPURINE
Pharmaceutical Form: Tablet

Primary Outcome(s)
Main Objective: To assess the effect of two withdrawal strategies over two years in patients with stable remission for more than 8 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
Primary end point(s): 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. This must be 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 abscess (size of at least 3 cm) or perianal abscess (size of at least 2 cm) (also considered as treatment failure, see below)
- 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 (under the predefined treatment strategy according to randomization) will be summed up within the first two years.
Secondary Objective: To identify baseline predictive factors of relapse in the three study groups. To assess in the three groups: the ability of blood CRP and fecal calprotectin to predict short term relapse in the the groups, time spent in clinical remission, the rate of treatment failure, the time to treatment failure, progression of bowel damage, the evolution of the disability score. To assess the safety and efficacy of infliximab retreatment in the antimetabolites group. To assess in the three study groups: safety, the health related quality of life, direct and indirect costs, evolution of blood CRP and fecal calprotectin. To assess evolution of infliximab trough levels and ATI in the two infliximab scheduled maintenance groups. To assess correlations between a series of biomarkers (proteomics, glycomics, DNA methylation, miRNA, metagenomics) and various clinical and biological outcomes. To assess the impact of 6TGN level on the various clinical and biological outcomes in the purine treated patients
Timepoint(s) of evaluation of this end point: 2 years
Secondary Outcome(s)
Secondary end point(s): - 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.
- Sustained clinical remission defined by CDAI<150 without steroids over two years.
- Treatment failure rate. Treatment failure is defined by not achieving remission after treatment adaptation following a relapse according to protocol (CDAI<150 or, in case of relapse defined by the occurrence of a new fistula, the absence of fistula closure, defined clinically by the persistence of an opened fistulous track and/or drainage upon gentle pressure). Treatment failure will also be defined by a major treatment side-effect leading to treatment cessation. The occurrence of an intra-abdominal or perianal abscess and the occurrence of an intestinal obstruction due to Crohn’s lesions and requiring a surgical resection or an endoscopic dilatation are also directly considered as treatment failure and will not be managed by treatment adaptation according to protocol.
- Time to treatment failure.
- Incidence and severity of acute or delayed infliximab infusion reaction. Severity of the acute infusion reaction wil be assessed according to Ring et Messmer classification (6).
- Tissue damage progression will be assessed by the Lémann Score absolute and relative change between baseline and end of the study (2 years).
- Other secondary judgement criteria: CDEIS/SES-CD, MaRIA score, CDMRIS, disability index, adverse events and SAE, events related to re-infusions, trough levels of infliximab, ATI, hsCRP, fecal calprotectin, direct medical costs, work productivity and activity index, short health scale, EQ-5D.
Timepoint(s) of evaluation of this end point: 2 years
Secondary ID(s)
2014-002311-41-FR
2014-3
NCT02177071
Source(s) of Monetary Support
GETAID
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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