We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Top Down Versus Step Up Strategies in Crohn's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00554710
Recruitment Status : Completed
First Posted : November 7, 2007
Last Update Posted : November 7, 2007
Centocor BV
Information provided by:
Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

Tracking Information
First Submitted Date  ICMJE November 6, 2007
First Posted Date  ICMJE November 7, 2007
Last Update Posted Date November 7, 2007
Study Start Date  ICMJE May 2001
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2007)
remission without corticosteroids and without surgical resection [ Time Frame: month 6 and 12 after inclusion ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2007)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Top Down Versus Step Up Strategies in Crohn's Disease
Official Title  ICMJE The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: infliximab+azathioprine
    infliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg
    Other Name: remicade/imuran
  • Drug: methylprednisolone or budesonide
    methylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper
    Other Name: Medrol, entocort, budenofalk
Study Arms  ICMJE
  • 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.
    Intervention: Drug: infliximab+azathioprine
  • 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.
    Intervention: Drug: methylprednisolone or budesonide
Publications * D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van De Mierop FJ, Coche JR, van der Woude J, Ochsenkuhn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-667. doi: 10.1016/S0140-6736(08)60304-9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 6, 2007)
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2004
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00554710
Other Study ID Numbers  ICMJE P01872
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Not Provided
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Centocor BV
  • Schering-Plough
Investigators  ICMJE
Principal Investigator: Geert R DHaens, MD, PhD Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
PRS Account Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
Verification Date November 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP