Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence.
Crohn Disease, Recurrence, Azathioprine
About this trial
This is an interventional prevention trial for Crohn Disease
Eligibility Criteria
Inclusion Criteria:
- Scheduled surgery for Crohn's disease (CD) with ileocolonic resection. Diagnosis of CD confirmed at least 4 months prior to surgery based on radiology and/or endoscopy.
- Having an increased risk for postoperative relapse for any of the following reasons: (1) active inflammatory disease with C-reactive protein level (CRP) elevated above 10 mg/L, or the use of antibiotics, steroids or biological therapy including infliximab for active ileal disease within 2 months before surgery which were administered for Crohn's disease and not for another unrelated intercurrent inflammatory or infectious disease; (2) perforating disease defined as the presence of entero-enteric or enterocutaneous fistulas or perivisceral abscess formation within 2 months before surgery. Perianal fistulizing disease will not be considered as an indication of perforating disease in the ileum or right-sided colon. (3) Previous ileo-colonic resection, (4) active smoking, (5) age below 30.
- Males and females 16-75 years old.
- Curative surgical resection. All macroscopically inflamed colonic segments (except for anorectal involvement) are to be removed at surgery. Stricturoplasties in small bowel segments not involving the anastomotic region are allowed.
- Patients able to start oral nutrition and oral therapy within 14 days from surgery.
- Patients able and willing to give written informed consent
- Women of childbearing potential should have a negative pregnancy test at inclusion.
Exclusion Criteria:
- Patients who only had strictureplasties or ileal/colonic resection without a new ileo-colonic anastomosis. Patients with ileorectal anastomosis.
- Patients with no increased risk of postoperative relapse as defined before.
- Patients with a known intolerance to azathioprine/6-mercaptopurine or with known homozygous thiopurine methyltransferase-low mutation.
- Patients in whom more than 100 cm of small bowel has been previously resected.
- Patients with active perianal disease or colorectal stenosis precluding ileocolonoscopy
- Patients with sepsis or other postoperative complications necessitating use of antibiotics for more than 14 days after surgery.
- Patients with liver test abnormalities (serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, bilirubin > 2 ULN), leucopenia (<3000 white blood cell count /µL, <1500 neutrophils /µL), thrombopenia with < 50.000 platelets/mm3.
- Patients with severe renal, pulmonary or cardiac disease.
- Pregnant or lactating women.
- Ongoing alcohol or substance abuse.
- Ongoing or recent (within 6 months) infectious disease (viral hepatitis, tuberculosis, AIDS, Herpes zoster related disease).
- Known malignancy 5 years from surgery except for superficial epithelioma of the skin with curative resection.
Sites / Locations
- Imelda Ziekenhuis
- UZ Leuven
- Univerzity Karlovy
- Evangelismos Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Systematic azathioprine group
Endoscopy-driven azathioprine group
Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.
Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102.