Top Down Versus Step Up Strategies in Crohn's Disease

NCT00554710 | Completed Phase 4

• 1 other identifier: P01872
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn's Disease

Keywords

Crohn's disease; immunomodulators; biologicals

Outcome Measures

Primary Outcomes (1)

• remission without corticosteroids and without surgical resection

  month 6 and 12 after inclusion

Secondary Outcomes (5)

• the time to relapse after successful induction therapy

  within 24 months

• the proportion of patients receiving infliximab, methylprednisolone and antimetabolites

  within 24 months

• the median serum C-reactive protein concentration

  24 months

• the proportion of patients experiencing adverse events

  24 months

• the mean endoscopic severity scores and the proportion of patients without ulcers

  after 24 months

Study Arms (2)

1

EXPERIMENTAL

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

2

ACTIVE COMPARATOR

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

Interventions

infliximab+azathioprine DRUG

infliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg

Also known as: remicade/imuran

1

methylprednisolone or budesonide DRUG

methylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper

Also known as: Medrol, entocort, budenofalk

2

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW: lead
• Centocor BV: collaborator
• Schering-Plough: collaborator

Study Sites (1)

Imelda GI Clinical Research Center

Bonheiden, 2820, Belgium

Location

Related Publications (1)

• 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.

  PMID: 18295023 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab; Azathioprine; Methylprednisolone; Budesonide

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes

Study Officials

• Geert R DHaens, MD, PhD

  Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 6, 2007
• First Posted: November 7, 2007
• Study Start: May 1, 2001
• Study Completion: January 1, 2004
• Last Updated: November 7, 2007

Record last verified: 2007-11

Locations

BE (1)