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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr. Falk Pharma GmbH
ClinicalTrials.gov Identifier:
NCT00946946
First received: July 24, 2009
Last updated: June 25, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Drug: Azathioprine
Drug: Mesalazine
Drug: Azathioprine placebo
Drug: Mesalazine placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Dr. Falk Pharma GmbH:

Primary Outcome Measures:
  • 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. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • endoscopic improvement at month 12, defined as ≥1 point reduction in Rutgeerts' score. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • change in CDAI score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 78
Study Start Date: February 2002
Study Completion Date: July 2009
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azathioprine
2.0-2.5 mg/kg/BW azathioprine tablets/day AND mesalazine placebo tablets
Drug: Azathioprine
2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets
Other Name: Azafalk 50mg tablets
Drug: Mesalazine placebo
2.0-2.5mg/kg/BW azathioprine /day and mesalazine placebo tablets
Active Comparator: Mesalazine
4g mesalazine tablets/day AND azathioprine placebo tablets
Drug: Mesalazine
4g Mesalazine tablets/day AND azathioprine placebo tablets
Other Name: Salofalk 500mg tablets
Drug: Azathioprine placebo
4g Mesalazine tablets/day AND azathioprine placebo tablets

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00946946

Locations
Austria
Universitaetsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie
Vienna, Austria, 1090
Germany
Robert-Bosch Krankenhaus, Innere Medizin I
Stuttgart, Germany, Postfach 501120
Sponsors and Collaborators
Dr. Falk Pharma GmbH
Investigators
Principal Investigator: Walter Reinisch, Prof Universitaetsklinik für Innere Medizin III, Abteilung Gastroenterologie and Hepatologie, Vienna, Austria
  More Information

Publications:
Responsible Party: Dr. Falk Pharma GmbH
ClinicalTrials.gov Identifier: NCT00946946     History of Changes
Other Study ID Numbers: AZT-2/CDP
Study First Received: July 24, 2009
Last Updated: June 25, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Dr. Falk Pharma GmbH:
Randomized
Crohn's Disease
Prevention
Azathioprine
mesalazine
mesalamine
TPMT

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Azathioprine
Mesalamine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 16, 2014