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

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2014-002311-41-FR
• Date of registration: 22/06/2015
• Prospective Registration: No
• 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: 12/08/2014
• 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

Countries of recruitment

France, Sweden, United Kingdom

Contacts

• Name: PATRICIADETRE
• Affiliation: GETAID

• Name: PATRICIADETRE
• 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 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:
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

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

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

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 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

Secondary Objective: 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. To assess the rate of treatment failure in the study groups. To assess the time to treatment failure in the study groups. To assess progression of bowel damage in the groups. To assess the safety and efficacy of infliximab retreatment in the antimetabolites group.To assess safety in the study groups. To assess the health related quality of life in the study groups. To assess direct and indirect costs in the study groups. To assess evolution of blood CRP and fecal calprotectin in the study groups. To assess evolution of infliximab trough levels and ATI in the 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

Timepoint(s) of evaluation of this end point: 2 years

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 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 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 occurence of a new fistula, the absence of fistula closure). The occurence of an intra-abdominal or peri-anal abcess and the occurence 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.
- Tissue damage progression will be assessed by the Lémann Score absolute and relative change between baseline and en of the study (2 years).
- Other secondary judgement criteria: 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 IBDQ

Timepoint(s) of evaluation of this end point: 2 years

Secondary ID(s)

2014-3

Source(s) of Monetary Support

GETAID