Clinical trial NCT00946946: Preventing Postoperative Relapse in Crohn's Disease Patients at Risk: Azathioprine Versus Mesalazine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Randomized
Crohn's Disease
Prevention
Azathioprine
mesalazine
mesalamine
TPMT
Lead sponsor: Dr. Falk Pharma GmbH
Sponsor class: INDUSTRY
First posted: 2009-07-27
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 12 months
Secondary outcomes:
measure: endoscopic improvement at month 12, defined as ≥1 point reduction in Rutgeerts' score.
timeFrame: 12 months
measure: change in CDAI score
timeFrame: 12 months
measure: adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Universitaetsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie
city: Stuttgart
country: Germany
facility: Robert-Bosch Krankenhaus, Innere Medizin I
Study officials:
affiliation: Universitaetsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie, Vienna, Austria
name: Walter Reinisch, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reinisch W, Angelberger S, Petritsch W, Shonova O, Lukas M, Bar-Meir S, Teml A, Schaeffeler E, Schwab M, Dilger K, Greinwald R, Mueller R, Stange EF, Herrlinger KR; International AZT-2 Study Group. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial. Gut. 2010 Jun;59(6):752-9. doi: 10.1136/gut.2009.194159.