Clinical trial NCT02247258: Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence.
Official title: Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence: Systematic Versus Endoscopic-directed Treatment. A Multi-center, Randomized, Clinical Practice Evaluation Study.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn Disease
Recurrence
Azathioprine
Prevention
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: International organization for the study of inflammatory bowel disease (IOIBD)
First posted: 2014-09-23
Enrollment: 63
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Endoscopic remission
timeFrame: Week 102
Secondary outcomes:
measure: Complete endoscopic remission
timeFrame: Week 102
measure: Absence of endoscopic relapse
timeFrame: Week 102
measure: Clinical remission
timeFrame: Week 102
measure: Sustained clinical remission
timeFrame: Week 102
measure: Radiological remission
timeFrame: Week 102
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
city: Leuven
country: Belgium
facility: UZ Leuven
city: Prague
country: Czech Republic
facility: Univerzity Karlovy
city: Athens
country: Greece
facility: Evangelismos Hospital
Study officials:
affiliation: UZ Leuven
name: Gert Van Assche, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferrante M, Papamichael K, Duricova D, D'Haens G, Vermeire S, Archavlis E, Rutgeerts P, Bortlik M, Mantzaris G, Van Assche G; International Organization for Study of Inflammatory Bowel Diseases. Systematic versus Endoscopy-driven Treatment with Azathioprine to Prevent Postoperative Ileal Crohn's Disease Recurrence. J Crohns Colitis. 2015 Aug;9(8):617-24. doi: 10.1093/ecco-jcc/jjv076. Epub 2015 Apr 29.