Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence.

NCT ID: NCT02247258

Last Updated: 2015-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2015-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Crohn Disease Recurrence Azathioprine Prevention

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Systematic 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.

Group Type ACTIVE_COMPARATOR

Azathioprine

Intervention Type DRUG

See arm/group descriptions

Ileocolonoscopy

Intervention Type PROCEDURE

See arm/group descriptions

Small bowel follow trough

Intervention Type PROCEDURE

See arm/group descriptions

Endoscopy-driven azathioprine group

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.

Group Type ACTIVE_COMPARATOR

Azathioprine in case of endoscopic recurrence

Intervention Type DRUG

See arm/group descriptions

Ileocolonoscopy

Intervention Type PROCEDURE

See arm/group descriptions

Small bowel follow trough

Intervention Type PROCEDURE

See arm/group descriptions

Interventions

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Azathioprine

See arm/group descriptions

Intervention Type DRUG

Azathioprine in case of endoscopic recurrence

See arm/group descriptions

Intervention Type DRUG

Ileocolonoscopy

See arm/group descriptions

Intervention Type PROCEDURE

Small bowel follow trough

See arm/group descriptions

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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International organization for the study of inflammatory bowel disease (IOIBD)

UNKNOWN

Sponsor Role collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gert Van Assche, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

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Imelda Ziekenhuis

Bonheiden, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Univerzity Karlovy

Prague, , Czechia

Site Status

Evangelismos Hospital

Athens, , Greece

Site Status

Countries

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Belgium Czechia Greece

References

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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.

Reference Type DERIVED
PMID: 25926532 (View on PubMed)

Other Identifiers

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ML3121

Identifier Type: -

Identifier Source: org_study_id