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

Crohn Disease Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02247258
• Other study ID #: ML3121
• Status: Terminated
• Phase: Phase 2
• First received: September 19, 2014
• Last updated: May 28, 2015
• Start date: October 2005
• Est. completion date: May 2015

Study information

• Verified date: September 2014
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics CommitteeBelgium: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 63
• Est. completion date: May 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Azathioprine
• Crohn Disease
• Prevention
• Recurrence

Intervention

Drug:
• Azathioprine
See arm/group descriptions
• Azathioprine in case of endoscopic recurrence
See arm/group descriptions

Procedure:
• Ileocolonoscopy
See arm/group descriptions
• Small bowel follow trough
See arm/group descriptions

Locations

Country	Name	City	State
Belgium	Imelda Ziekenhuis	Bonheiden
Belgium	UZ Leuven	Leuven
Czech Republic	Univerzity Karlovy	Prague
Greece	Evangelismos Hospital	Athens

Sponsors (2)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven	International organization for the study of inflammatory bowel disease (IOIBD)

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endoscopic remission	The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks	Week 102	No
Secondary	Complete endoscopic remission	The percentage of patients with a Rutgeerts' score of i0 at 102 weeks	Week 102	No
Secondary	Absence of endoscopic relapse	The percentage of patients with a Rutgeerts' score of i0-i2 at 102 weeks	Week 102	No
Secondary	Clinical remission	The percentage of patients in clinical remission (Crohn's disease activity index, CDAI <150) at 102 weeks	Week 102	No
Secondary	Sustained clinical remission	Crohn's disease activity index, CDAI < 150 throughout the 102 weeks study period	Week 102	No
Secondary	Radiological remission	The percentage of patients with radiological remission at 102 weeks.	Week 102	No