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Top Down Versus Step Up Strategies in Crohn's Disease

This study has been completed.
Sponsor:
Collaborators:
Centocor BV
Schering-Plough
Information provided by:
Belgian IBD Research Group
ClinicalTrials.gov Identifier:
NCT00554710
First received: November 6, 2007
Last updated: NA
Last verified: November 2007
History: No changes posted
  Purpose

The study prospectively compares two treatment algorithms for newly diagnosed Crohn's disease: one 'aggressive' treatment with early introduction of immunomodulators and biologicals and one 'standard treatment' with corticosteroids and only later introduction of immunosuppressives and biologicals if disease activity requires that.


Condition Intervention Phase
Crohn's Disease
Drug: infliximab+azathioprine
Drug: methylprednisolone or budesonide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux

Resource links provided by NLM:


Further study details as provided by Belgian IBD Research Group:

Primary Outcome Measures:
  • remission without corticosteroids and without surgical resection [ Time Frame: month 6 and 12 after inclusion ]

Secondary Outcome Measures:
  • the time to relapse after successful induction therapy [ Time Frame: within 24 months ]
  • the proportion of patients receiving infliximab, methylprednisolone and antimetabolites [ Time Frame: within 24 months ]
  • the median serum C-reactive protein concentration [ Time Frame: 24 months ]
  • the proportion of patients experiencing adverse events [ Time Frame: 24 months ]
  • the mean endoscopic severity scores and the proportion of patients without ulcers [ Time Frame: after 24 months ]

Enrollment: 129
Study Start Date: May 2001
Study Completion Date: January 2004
Arms Assigned Interventions
Experimental: 1
Patients received three infusions of infliximab 5 milligrams per kilogram (weeks 0, 2 and 6) in combination with azathioprine 2-2.5 milligrams per kilogram per day from day 0 onwards. If the patients responded and tolerated both drugs, azathioprine was continued for the duration of the trial. Patients who were intolerant to azathioprine received methotrexate at an initial dose of 25 milligrams administered subcutaneously each week for 12 weeks with dose reduction to 15 milligrams per week thereafter. Following initial therapy, patients who developed worsening symptoms were retreated with additional infusions of infliximab. If symptoms persisted methylprednisolone was initiated and azathioprine or methotrexate was continued.
Drug: infliximab+azathioprine
infliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg
Other Name: remicade/imuran
Active Comparator: 2
Induction with methylprednisolone (MP) or budesonide (BUD): MP 32 mg/day for 3 weeks was followed by tapering by 4 mg per week to 0; BUD 9 mg per day for 8 weeks with tapering to 0 by 3 mg per week thereafter.Patients who worsened during the tapering had the dose increased to the initial dose and tapered again. If patients worsened, azathioprine (2-2.5 mg per day) was introduced. Patients who relapsed following withdrawal of steroids received a second course in combination with azathioprine. For patients who failed 4 weeks of steroids, MP dose was given at 64 mg/day for 2 weeks, tapered by 8 mg per week; azathioprine was added. Patients who remained symptomatic despite 16 weeks of azathioprine received infliximab (5 mg/kg IV at weeks 0, 2 and 6). Patients who relapsed despite methotrexate or those intolerant to both azathioprine and methotrexate also received infliximab, without antimetabolite therapy. Infliximab was repeated upon relapse of symptoms in these patients.
Drug: methylprednisolone or budesonide
methylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper
Other Name: Medrol, entocort, budenofalk

Detailed Description:

This two year open-label randomized trial compares the early use of combined immunosuppression to conventional management in patients with active Crohn's disease who have not previously received glucocorticoids, antimetabolites, or infliximab. Patients assigned to combined immunosuppression receive azathioprine and 3 infusions of 5 milligrams per kilogram of body weight of infliximab at weeks 0, 2, and 6. Retreatment with infliximab and, if ultimately necessary, corticosteroids are used to control disease activity. Patients assigned to conventional management receive corticosteroids followed, in sequence, by azathioprine and infliximab. The primary outcome measure is remission without corticosteroids and without bowel resection at weeks 26 and 52.

  Eligibility

Ages Eligible for Study:   16 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age 16 - 75 years
  • diagnosis of Crohn's disease within the past 4 years
  • no previous treatment with corticosteroids, antimetabolites, or biologic agents.
  • Active Crohn's disease, defined by a Crohn's Disease Activity Index (CDAI)20 score of greater than 200 points for a minimum of 2 weeks prior to randomization.

Exclusion Criteria:

  • immediate need for surgery
  • symptomatic stenosis or ileal/colonic strictures with prestenotic dilatation;
  • signs, symptoms or laboratory tests indicating severe, medical disease;
  • documented chronic infection
  • a positive stool culture for pathogens
  • a positive tuberculin test or a chest radiograph consistent with tuberculosis.
  • malignancy
  • allergy to murine proteins
  • pregnancy
  • substance abuse
  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: NCT00554710

Locations
Belgium
Imelda GI Clinical Research Center
Bonheiden, Belgium, 2820
Sponsors and Collaborators
Belgian IBD Research Group
Centocor BV
Schering-Plough
Investigators
Principal Investigator: Geert R DHaens, MD, PhD Belgian IBD Research Group
  More Information

No publications provided by Belgian IBD Research Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00554710     History of Changes
Other Study ID Numbers: P01872
Study First Received: November 6, 2007
Last Updated: November 6, 2007
Health Authority: Belgium: Institutional Review Board

Keywords provided by Belgian IBD Research Group:
Crohn's disease
immunomodulators
biologicals

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Azathioprine
Budesonide
Infliximab
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Analgesics
Analgesics, Non-Narcotic
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Bronchodilator Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 20, 2014