Azathioprine, Crohn Disease, Prevention, Recurrence
Conditions
Brief summary
The objective of this study is to evaluate if in the prevention of postoperative recurrence of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by endoscopic criteria. The primary endpoint, disease recurrence, encompasses symptomatic and surgical recurrence as well as severe endoscopic lesions at the final, 2 year, assessment.
Interventions
DRUGAzathioprine
See arm/group descriptions
DRUGAzathioprine in case of endoscopic recurrence
See arm/group descriptions
PROCEDUREIleocolonoscopy
See arm/group descriptions
PROCEDURESmall bowel follow trough
See arm/group descriptions
Sponsors
International organization for the study of inflammatory bowel disease (IOIBD)
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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. 3. Males and females 16-75 years old. 4. 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. 5. Patients able to start oral nutrition and oral therapy within 14 days from surgery. 6. Patients able and willing to give written informed consent 7. Women of childbearing potential should have a negative pregnancy test at inclusion.
Exclusion criteria
1. Patients who only had strictureplasties or ileal/colonic resection without a new ileo-colonic anastomosis. Patients with ileorectal anastomosis. 2. Patients with no increased risk of postoperative relapse as defined before. 3. Patients with a known intolerance to azathioprine/6-mercaptopurine or with known homozygous thiopurine methyltransferase-low mutation. 4. Patients in whom more than 100 cm of small bowel has been previously resected. 5. Patients with active perianal disease or colorectal stenosis precluding ileocolonoscopy 6. Patients with sepsis or other postoperative complications necessitating use of antibiotics for more than 14 days after surgery. 7. 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. 8. Patients with severe renal, pulmonary or cardiac disease. 9. Pregnant or lactating women. 10. Ongoing alcohol or substance abuse. 11. Ongoing or recent (within 6 months) infectious disease (viral hepatitis, tuberculosis, AIDS, Herpes zoster related disease). 12. Known malignancy 5 years from surgery except for superficial epithelioma of the skin with curative resection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic remission | Week 102 | The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete endoscopic remission | Week 102 | The percentage of patients with a Rutgeerts' score of i0 at 102 weeks |
| Absence of endoscopic relapse | Week 102 | The percentage of patients with a Rutgeerts' score of i0-i2 at 102 weeks |
| Clinical remission | Week 102 | The percentage of patients in clinical remission (Crohn's disease activity index, CDAI \<150) at 102 weeks |
| Sustained clinical remission | Week 102 | Crohn's disease activity index, CDAI \< 150 throughout the 102 weeks study period |
| Radiological remission | Week 102 | The percentage of patients with radiological remission at 102 weeks. |
Countries
Belgium, Czechia, Greece
Outcome results
None listed