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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: 17 August 2015
Main ID:  EUCTR2014-002311-41-GB
Date of registration: 30/06/2015
Prospective Registration: Yes
Primary sponsor: University of Edinburgh
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
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 (SPARE) - SPARE
Date of first enrolment: 14/07/2015
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 Other specify the comparator: Combination therapy versus monotherapy with either infliximab or antimetabolites Number of treatment arms in the trial: 3  
Phase: 
Countries of recruitment
Belgium France Germany Sweden United Kingdom
Contacts
Name: Ray French    
Address:  The Queen's Medical Research Institute EH16 4TJ Edinburgh United Kingdom
Telephone: 01312429461
Email: researchgovernance@ed.ac.uk
Affiliation:  University of Edinburgh
Name: Ray French    
Address:  The Queen's Medical Research Institute EH16 4TJ Edinburgh United Kingdom
Telephone: 01312429461
Email: researchgovernance@ed.ac.uk
Affiliation:  University of Edinburgh
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 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Luminal Crohn's disease patients in steroid free remission for at least 6 months and on combination therapy with infliximab and antimetabolites for at least 1 year
MedDRA version: 18.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]
Intervention(s)

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

Trade Name: Imuran
Product Name: Azathioprine
Pharmaceutical Form: Tablet

Trade Name: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Concentrate and solvent for cutaneous solution

Trade Name: Mercaptopurine
Product Name: Mercaptopurine
Pharmaceutical Form: Tablet

Primary Outcome(s)
Main Objective: To demonstrate that Infliximab scheduled maintenance with or without antimetabolites is superior (better) to antimetabolites alone to maintain sustained steroid-free remission over 2 years, while the latter is non inferior (not any worse) with regards to the mean time spent in remission over the same duration
Primary end point(s): There are 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.

Secondary Objective: - To identify baseline predictive factors of relapse in the three study groups.
- To assess the ability of blood C-reactive protein (CRP) and fecal calprotectin to predict short term relapse in the three groups.
- To assess time spent in clinical 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 antibodies to infliximab (ATI) in the two infliximab scheduled maintenance groups.
- To assess
Timepoint(s) of evaluation of this end point: 2 years
Secondary Outcome(s)
Secondary end point(s): - 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
Timepoint(s) of evaluation of this end point: 2 years
Secondary ID(s)
2014-002311-41-FR
2014-3
Source(s) of Monetary Support
European Union
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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