Infliximab for the Prevention of Recurrent Crohn's Disease After Surgery

Phase 4

Completed

Conditions: Crohn's Disease

Interventions: Drug: infliximab
Drug: placebo

Registration Number: NCT00688636

Lead Sponsor: University of Pittsburgh

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	infliximab	-
2	placebo	-

Primary Outcome Measures

Name	Time	Method
Endoscopic Recurrence: the Proportion of Patients in Endoscopic Recurrence at One Year	one year	Endoscopic recurrence was defined as i2,i3,i4. We used the Rutgeerts' Endoscopic Scoring System. Scores as follows i0, no lesions; i1, 5 or fewer aphthous lesions; i2, more than 5 aphthous lesions with normal mucosa between the lesions or skip areas of larger lesions or lesions confined to the ileocolonic anastomosis; i3, diffuse, aphthous ileitis with diffusely inflamed mucosa; and i4, diffuse inflammation with large ulcers, nodules, and/or narrowing. Endoscopic recurrence was defined as i2,i3,i4 and endoscopic remission was defined as i0 or i1.

Secondary Outcome Measures

Name	Time	Method
Clinical Recurrence at One Year: Defined by Crohn's Disease Activity Index (CDAI) > 200	One year	The Crohn's Disease Activity Index (CDAI) is calculated by a measurement of symptoms, signs, and lab tests over a time period of the previous 7 days. The CDAI includes: Number of very soft stools; sum of abdominal pain ratings: (0=none, 1= mild, 2=moderate, 3=severe); general well being (0=well, 1=slightly below par, 2=poor, 3=very poor, 4=terrible); Symptoms or findings presumed related to Crohn's disease (present): arthritis or arthralgia, iritis or uveitis, erythema nodosum, pyoderma gangrenosum, aphthous stomatitis, anal fissure, fistula or perirectal abscess, other bowel related fistula, febrile episode over 100 degrees during past week, taking lomotil or opiates for diarrhea, abnormal mass (0=none; 0.4=questionable; 1=present) hematocrit \[(typical-current) X 6\] Normal average male = 47, female =42, body weight
Mean Erythrocyte Sedimentation Rate	one year	erythrocyte sedimentation rate value - blood test
Histological Recurrence of Crohn's Disease as Determined From Biopsies of Neo-terminal Ileum Above the Ileocolonic Anastomosis	One year	Histologic recurrence based on a histologic activity score and the presence of polymononuclear cells. The maximum score is 14 per biopsy site.
C-reactive Protein Concentration as a Surrogate Marker of Inflammation	one year	The CRP was obtained at each study visit as a surrogate marker of inflammation. The CRP was recorded as milligram per deciliter (mg/dl). A normal CRP was 0-0.8 mg/dl; levels exceeding 0.8 mg/dl indicated inflammation.