Clinical trial NCT00554710: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Crohn's disease
immunomodulators
biologicals
Lead sponsor: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
Sponsor class: OTHER
Collaborators: name: Centocor BV
name: Schering-Plough
First posted: 2007-11-07
Enrollment: 129
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: remission without corticosteroids and without surgical resection
timeFrame: month 6 and 12 after inclusion
Secondary outcomes:
measure: the time to relapse after successful induction therapy
timeFrame: within 24 months
measure: the proportion of patients receiving infliximab, methylprednisolone and antimetabolites
timeFrame: within 24 months
measure: the median serum C-reactive protein concentration
timeFrame: 24 months
measure: the proportion of patients experiencing adverse events
timeFrame: 24 months
measure: the mean endoscopic severity scores and the proportion of patients without ulcers
timeFrame: after 24 months
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda GI Clinical Research Center
Study officials:
affiliation: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
name: Geert R DHaens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.