Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing REMICADE (infliximab) and Placebo in the Prevention of Recurrence in Crohn’s Disease Patients Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence - PREVENT

• Register: EUCTR
• Last refreshed on: 14 September 2015
• Main ID: EUCTR2010-018431-18-IT
• Date of registration: 10/01/2011
• Prospective Registration: No
• Primary sponsor: CENTOCOR
• Public title: Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing REMICADE (infliximab) and Placebo in the Prevention of Recurrence in Crohn’s Disease Patients Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence - PREVENT
• Scientific title: Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing REMICADE (infliximab) and Placebo in the Prevention of Recurrence in Crohn’s Disease Patients Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence - PREVENT
• Date of first enrolment: 03/12/2010
• Target sample size: 290
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018431-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Man or woman 18 years of age or older 2.Are considered eligible according to the following TB screening criteria: a. Have no history of latent or active TB prior to screening. An exception is made for patients with a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation. b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination. c. Have no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent. 4.Have undergone an ileocolonic surgical resection (i.e. an intestinal resection with an ileocolonic anastomosis). 5.Patients must also be at an increased risk of recurrence of active CD, as defined by at least ONE of the following: a.The qualifying surgery was the patient’s second intra-abdominal operation for CD in the past 10 years b.The qualifying surgery was the patient’s third (or more) intra-abdominal operation for CD c.The qualifying surgery was performed for a penetrating complication of CD (i.e. an intra-abdominal abscess, internal fistula, sinus tracts or intestinal perforation) d.The patient has any history of perianal fistulizing CD provided that this has not been active in the 3 months prior to study start e.The patient is a cigarette smoker (defined as currently smoking and having smoked an average of at least 10 cigarettes a day for the past year or more) and has been unable or unwilling to quit smoking despite counseling to stop smoking 6.Patients must meet the following criteria with respect to prior treatment with an anti-TNF agent: a.Started an anti-TNF agent for the first time within 1 year prior to surgery and received the last dose of the anti-TNF agent within 4 months or less of having surgery AND b.Have not previously discontinued any anti-TNF agent as a result of tolerability issues OR c.Be na?ve to treatment with an anti-TNF agent 7.Are able to adhere to the following concomitant medication requirements: a.Patients who are receiving treatment with an immunomodulator (AZA, 6-MP, or MTX) prior to surgery may continue on this medication but must be on a stable dose by 4 weeks after their surgery and should remain on that dose for the duration of the study, unless discontinuation or a dose decrease is warranted for safety or tolerability reasons. Patients who are not taking an immunomodulator prior to surgery should not initiate an immunomodulator after surgery or at any time during the study. Patients may have discontinued immunomodulators at any time prior to the start of the study. (complete and more detailed list of inclusion criteria can be found at point 4.2 of study protocol).
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criterion 2 for information regarding eligibility with a history of latent TB 2. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening 3. Have a chest radiograph within 3 months prior to the first infusion of study agent that shows a clinically significant abnormality, such as a malignancy or infection, or any abnormalities suggestive of TB 4. Have had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to screening 5. Have initial and repeat indeterminate QuantiFERON-TB Gold test results 6. Are considered ineligible according to the TB eligibility assessment, screening and early detection of reactivation rules 7. Have macroscopically active CD which was not resected at the time of surgery 8. Have had any active perianal disease in the past 3 months (except skin tags) or have had any draining fistula within the past 3 months 9. Have evidence of active CD in regions beyond the site of surgery in the GI tract within 1 year of the time of enrollment 10. Do not meet the criteria for being at an increased risk of postoperative recurrence of active CD as outlined in the inclusion criteria. 11. Have an ostomy or stoma 12. Have a qualifying surgery with postoperative complications such as, but not limited to, postoperative intra-abdominal abscess, wound dehiscense, anastomotic leak, the need for a second operation, pulmonary embolus, or serious infection. 13. Have documented short bowel syndrome (more than 100 cm in total of small bowel resected) 14. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter 15. Have shown a previous immediate hypersensitivity response, including anaphylaxis, to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody) 16. Have a known allergy to murine proteins or other chimeric proteins 17. Have received within 3 months prior to screening or are expected to receive any live viral (e.g., small-pox) or live bacterial vaccinations during the trial or up to 3 months after the last administration of study agent 18. Have evidence of an active infection at the time of randomization or have had a serious infection not related to CD within 6 months prior to screening 19. Have had a Clostridium difficile (C. difficile) infection within the past 4 months 20. Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening (complete and more detailed list of exclusion criteria can be found at point 4.3 of study protocol)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn`s disease (DS)
MedDRA version: 9.1 Level: LLT Classification code 10011401

Intervention(s)

Trade Name: REMICADE
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Powder for infusion*
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The primary objective of this study will be to compare the efficacy of infliximab with that of placebo in the prevention of clinical recurrence of CD through Week 76, defined as a composite endpoint that requires endoscopic confirmation of recurrence, in patients who are at an increased risk of active CD recurrence following ileocolonic resection.

Primary end point(s): The primary endpoint is clinical recurrence of CD through Week 76. Clinical recurrence is a composite endpoint defined by the following: • A = 70-point increase from baseline in CDAI; and • A CDAI score of = 200; and • Evidence of endoscopic recurrence. Endoscopic recurrence is defined as a Rutgeerts score of = i2 at the anastomotic site or its equivalent elsewhere in the GI tract. Patients who meet the criteria for clinical recurrence at Week 76 or at any timepoint prior to Week 76 will be considered to have clinical recurrence through Week 76. Patients who initiate a prohibited CD-related medication or have a prohibited use of a CD medication prior to Week 76 will be considered to have had clinical recurrence.

Secondary Objective: The major secondary objective will be to compare the efficacy of infliximab with that of placebo in the prevention of endoscopic recurrence of CD through Week 76, defined as a Rutgeerts score = i2 either at the anastomosis or elsewhere in the gastrointestinal [GI] tract, in patients who are at an increased risk of active CD recurrence following ileocolonic resection.

Secondary ID(s)

2010-018431-18-DE

REMICADECRD3001