Clinical trial NCT00688636: Infliximab for the Prevention of Recurrent Crohn's Disease After Surgery
Official title: Infliximab for the Prevention of Recurrent Crohn's Disease After Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Crohn's Disease
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Centocor, Inc.
First posted: 2008-06-03
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: A randomized, placebo-controlled pilot study to determine endoscopic recurrence of Crohn's disease 12 months after curative, resective ileal or ileocolonic surgery in patients receiving post-operative infliximab or placebo


Eligibility criteria: Inclusion Criteria:

* men/women \> 18 years of age
* curative resection/ileocolonic anastomosis for Crohn's disease
* may have received previously received infliximab
* if on oral aminosalicylates or corticosteroids, dose must be stable for 4 weeks prior to surgery
* if on 6-mercaptopurine,azathioprine or methotrexate,individual must have been on it for minimum of 3 months prior to surgery with stable dose for 4 weeks
* men and women must use adequate birth control for duration of study and for 6 months after receiving the last infusion
* antibiotics for treatment of Crohn's disease must be discontinued within 12 weeks after surgery; antibiotics are allowable throughout study as long as primary purpose of antibiotic therapy is not for primary treatment of Crohn's disease
* screening lab results must meet screening criteria (hemoglobin = or \> 8.5g/dL; Serum glutamic oxaloacetic transaminase ,3 times upper normal limit,platelets =or\> 100 x 10 9th/L; lymphocytes count =or\> 0.5 x 10 9th/L and neutrophils =or\> 1.0 x 10 9th/L
* have a documented negative reaction to a purified protein derivative skin test performed within 3 months prior to baseline
* have a normal chest radiograph results within 3 months prior to baseline
* are capable of providing written informed consent and obtained prior to conducting any protocol-specified procedures
* willing to adhere to the study visit schedule and other protocol requirements
* are considered eligible according to the tuberculosis eligibility assessment, screening and early detection of reactivation rules
* patients who undergo resective surgery and primary ileocolonic anastomosis with a temporary ileostomy upon takedown of the diverting ileostomy.

Exclusion Criteria:

* patients with greater than 10 years of Crohn's disease requiring first resection of a short (\<10cm) fibrostenotic stricture
* macroscopically active disease at anastomosis at time of surgery
* presence of stoma
* prior severe infusion reaction to infliximab
* history of anaphylaxis to murine products or other chimeric proteins
* any of the following medications taken within 12 weeks of surgery: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, investigational drugs, or medications targeted at reducing tumor necrosis factor
* have a positive stool culture for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin and have clinically significant signs of an enteric infection at screening
* women who are pregnant, nursing or planning pregnancy during the trial or within 6 months after the last infusion
* patient with active tuberculosis, patient newly diagnosed with latent tuberculosis who's receiving tuberculosis prophylaxis, patient with recent close contact to individual with active tuberculosis
* have or have had opportunistic infection within 6 months of screening
* have chest radiograph within 3 months prior to screening that shows malignancy, infection, or abnormalities suggestive of tuberculosis
* documentation of seropositive for HIV
* documentation of a positive test for hepatitis B surface antigen or a history of documented hepatitis C
* have current signs/symptoms of systemic lupus erythematosus, or severe progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral diseases
* presence of a transplanted solid organ (with exception of corneal transplant \> 3 months prior to randomization)
* Have any current or known malignancy or have history of malignancy within 5 years of screening(except for squamous or basal cell carcinoma of the skin that has been fully excised with no evidence of recurrence)
* have history of lymphoproliferative disease or splenomegaly
* have known substance abuse(drug/alcohol)/dependency within the previous 3 years, history of noncompliance with medical regimens, or other condition that may interfere with adherence to protocol requirements
* are unwilling/unable to undergo multiple venipunctures because of poor tolerability or lack of easy access
* known history of demyelinating disease
* a chronic or recurrent infectious disease
* serious infection, hospitalization for infection, or treatment with IV antibiotics for infection within 2 months prior to randomization
* a serious concomitant illness that may interfere with participation in trial
* concomitant diagnosis/history of congestive heart failure
* current use of prescription doses or chronic/frequent use of non-steroidal anti-inflammatory drugs
* ulcerative colitis
* concurrent participation in another investigative trial
* use of any investigational drug within 30 days prior to randomization

Primary outcomes:
measure: Endoscopic Recurrence: the Proportion of Patients in Endoscopic Recurrence at One Year
timeFrame: one year
Secondary outcomes:
measure: Clinical Recurrence at One Year: Defined by Crohn's Disease Activity Index (CDAI) > 200
timeFrame: One year
measure: Histological Recurrence of Crohn's Disease as Determined From Biopsies of Neo-terminal Ileum Above the Ileocolonic Anastomosis
timeFrame: One year
measure: C-reactive Protein Concentration as a Surrogate Marker of Inflammation
timeFrame: one year
measure: Mean Erythrocyte Sedimentation Rate
timeFrame: one year
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Miguel D Regueiro, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology. 2009 Feb;136(2):441-50.e1; quiz 716. doi: 10.1053/j.gastro.2008.10.051. Epub 2008 Oct 31.