Preventing Postoperative Relapse in Crohn's Disease Patients at Risk: Azathioprine Versus Mesalazine

Study Overview
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Brief Summary
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This study aims to compare azathioprine versus mesalazine tablets for the prevention of clinical relapse in postoperative Crohn's disease (CD) patients with moderate or severe endoscopic recurrence.

Official Title
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Double-blind, Double-dummy, Randomised, Multicentre, Comparative Study on the Efficacy and Safety of Azathioprine Versus Mesalazine for Prevention of Clinical Relapses in Crohn's Disease Patients With Postoperative Moderate or Severe Endoscopic Recurrence

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Azathioprine
* Drug: Mesalazine
* Drug: Azathioprine placebo
* Drug: Mesalazine placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent, Man or woman between 18 and 70 years of age, Diagnosis of Crohn's disease confirmed by endoscopic and histological, or endoscopic and radiological criteria within one year or by histopathological criteria during resection, Clinical remission defined as Crohn´s Disease Activity Index (CDAI) < 200, within the last two weeks. No clinical relapse due to Crohn's disease since resection, Moderate (i2a) or severe endoscopic recurrence (i3-i4) within 6 to 24 months after curative resection of the terminal ileum and partial colectomy with ileocolonic resection for complications of ileal Crohn´s disease and with a construction of an ileocolonic anastomosis, Within the neoterminal ileum at least more than 5 aphthous lesions with normal mucosa between the lesions, or skip areas of larger lesions, Negative pregnancy test at screening visit in females of childbearing potential, Use of appropriate contraceptive methods for females of childbearing potential and males with procreative capacity during treatment and at least up to 3 months after the end of treatment. Exclusion Criteria: Lesions confined to the ileocolonic anastomosis (i.e., < 1 cm in length) Short bowel syndrome, Serious secondary illnesses of an acute or chronic nature, which in the opinion of the Investigator renders the patient unsuitable for inclusion into the study, Serum creatinine levels exceeding 1.5 mg/dL or 130 umol/L, Presence of an ileo-/colonic stoma, Genotype: thiopurine methyltransferase (TPMT) -/-, Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years), Treatment with cytostatics or immunosuppressants, methotrexate, cyclosporine, 6-MP, Azathioprine, 6-TG or anti-TFN-alpha therapy since resection; postoperative treatment with corticosteroids for more than 4 weeks or postoperative treatment with oral antibiotics (e.g., metronidazole, ciprofloxacin) for more than 4 weeks, Application of non-steroidal anti-inflammatory drugs (NSAIDS) within 2 weeks before Screening visit except low dose acetylsalicylic acid and except paracetamol, Known intolerance/hypersensitivity to study drugs or drugs of similar chemical structure or pharmacological profile, Scheduled or intended active immunisation with living vaccines within the next 12 months, Well-founded doubt about the patient's cooperation, Existing pregnancy, lactation, or intended pregnancy or impregnation within the next 15 months, Non-use of appropriate contraceptives in males with procreative capacity and females of childbearing potential (e.g. condoms for males, intrauterine device [IUD], hormonal contraception for females, or a means of contraception for a particular patient considered adequate by the responsible investigator) during treatment and within 3 months after the end of treatment, Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial, Present stricture plasty (no exclusion if the present stricture plasty was macroscopically without any relevant finding of inflammation seen during index surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azathioprine<br>2.0-2.5 mg/kg/BW azathioprine tablets/day AND mesalazine placebo tablets | Drug: Azathioprine<br>* 2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets<br>* Other names: Azafalk 50mg tablets;Drug: Mesalazine placebo<br>* 2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets<br>|
| Active Comparator: Mesalazine<br>4g mesalazine tablets/day AND azathioprine placebo tablets | Drug: Mesalazine<br>* 4g Mesalazine tablets/day AND azathioprine placebo tablets<br>* Other names: Salofalk 500mg tablets;Drug: Azathioprine placebo<br>* 4g Mesalazine tablets/day AND azathioprine placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint was therapeutic failure at one year, defined as CDAI score ≥200 and an increase of ≥60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endoscopic improvement at month 12, defined as ≥1 point reduction in Rutgeerts' score. |  | 12 months | 
| change in CDAI score |  | 12 months | 
| adverse events |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized, Crohn's Disease, Prevention, Azathioprine, mesalazine, mesalamine, TPMT