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

NCT02247258 | Terminated Phase 2

• 1 other identifier: ML3121
• Study Type: interventional
• Target: 63
• Locations: 3 countries
• Sites: 4

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.

Conditions

Crohn Disease; Recurrence; Azathioprine; Prevention

Outcome Measures

Primary Outcomes (1)

• Endoscopic remission

  The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks

  Week 102

Secondary Outcomes (5)

• Complete endoscopic remission

  Week 102

• Absence of endoscopic relapse

  Week 102

• Clinical remission

  Week 102

• Sustained clinical remission

  Week 102

• Radiological remission

  Week 102

Study Arms (2)

Systematic azathioprine group

ACTIVE COMPARATOR

Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks.

Drug: Azathioprine; Procedure: Ileocolonoscopy; Procedure: Small bowel follow trough

Endoscopy-driven azathioprine group

ACTIVE COMPARATOR

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.

Drug: Azathioprine in case of endoscopic recurrence; Procedure: Ileocolonoscopy; Procedure: Small bowel follow trough

Interventions

Azathioprine DRUG

See arm/group descriptions

Systematic azathioprine group

Azathioprine in case of endoscopic recurrence DRUG

See arm/group descriptions

Endoscopy-driven azathioprine group

Ileocolonoscopy PROCEDURE

See arm/group descriptions

Endoscopy-driven azathioprine group; Systematic azathioprine group

Small bowel follow trough PROCEDURE

See arm/group descriptions

Endoscopy-driven azathioprine group; Systematic azathioprine group

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• International organization for the study of inflammatory bowel disease (IOIBD): collaborator

Study Sites (4)

Imelda Ziekenhuis

Bonheiden, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Univerzity Karlovy

Prague, Czechia

Location

Evangelismos Hospital

Athens, Greece

Location

Related Publications (1)

• 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.

  PMID: 25926532 DERIVED

MeSH Terms

Conditions

Crohn Disease; Recurrence

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gert Van Assche, MD PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2014
• First Posted: September 23, 2014
• Study Start: October 1, 2005
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2015
• Last Updated: May 29, 2015

Record last verified: 2014-09

Locations

CZ (1); GR (1); BE (2)