Top Down Versus Step Up Strategies in Crohn's Disease

• ClinicalTrials.gov Identifier: NCT00554710
• Recruitment Status: Completed
• First Posted: November 7, 2007
• Last Update Posted: November 7, 2007
• Sponsor: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
• Collaborators: Centocor BV; Schering-Plough
• Information provided by: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

Tracking Information

• First Submitted Date: November 6, 2007
• First Posted Date: November 7, 2007
• Last Update Posted Date: November 7, 2007
• Study Start Date: May 2001
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: November 6, 2007): remission without corticosteroids and without surgical resection [ Time Frame: month 6 and 12 after inclusion ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Top Down Versus Step Up Strategies in Crohn's Disease
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 6, 2007): 129
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: January 2004
• Primary Completion Date: Not Provided

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT00554710
• Other Study ID Numbers: P01872
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
• Original Study Sponsor: Same as current

Collaborators

• Centocor BV
• Schering-Plough

Investigators

• 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