The ideal management of Crohn's disease: top-down versus step-up strategies - a prospective controlled trial in the Benelux

Completed

Conditions: Crohn's disease
Digestive System
Crohn's disease [regional enteritis]

Registration Number: ISRCTN61510219

Lead Sponsor: Academic Medical Centre (AMC) (The Netherlands)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 130

Inclusion Criteria

1. Men and women aged 16 - 75 years
2. New diagnosis of Crohn's disease (CD), endoscopically and histologically or radiologically (in the case of small bowel disease) proven or diagnosis of Crohn's disease in the previous 4 years but never treated with corticosteroids/budesonide or immunomodulators (azathioprine/6-mercaptopurine/methotrexate/cyclosporin/tacrolimus [FK 506]/mycophenolate mofetil) or biologics (Remicade® or any other investigational drugs)
3. Clinical Disease Activity Index (CDAI) greater than 200 for more than four weeks (to exclude self-limited problems) in new patients or greater than 200 for more than two weeks for patients with known CD
4. Symptoms do not improve with 5-aminosalicylic acid (5-ASA) therapy in appropriate doses (Pentasa® 4 g per day for 6 weeks) or are considered too serious to be treated with 5-ASA alone. Antibiotics can be given at the discretion of the investigator.
5. Willing to sign the informed consent form
6. Ability to comply with study visits and other protocol requirements
7. Women of childbearing potential must be willing to use adequate birth control measures in the 6 month period following each infliximab infusion. If pregnant, they will be excluded from further infliximab infusions.

Exclusion Criteria

1. Need for surgery at diagnosis or in the immediate future: complications such as abdominal abscess or stricture with obstruction
2. Current signs or symptoms of severe, uncontrolled or progressive renal, hepatic, haematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease
3. Serious infections such as viral hepatitis, pneumonia, pyelonephritis in the last 3 months
4. Recent or ongoing tuberculosis (less than 2 years) or treatment for tuberculosis
5. Less serious infections should be treated appropriately, after which the patient can be included upon the discretion of the investigator
6. Use of biologics, corticosteroids or immunemodulators for other diseases
7. Documented human immunodeficiency virus (HIV) infection
8. Any currently known malignancy or premalignant lesion or any history of malignancy in the last 5 years
Active pregnancy or immediate pregnancy wish; pregnancy should be deferred until at least 6 months after the last infliximab infusion
9. Patient on azathioprine have to continue this medication should they become pregnant during the study
10. Allergy to murine proteins
11. Known recent substance abuse (drugs or alcohol)
12. Symptomatic stenosis or ileal/colonic strictures with prestenotic dilatation
13. Positive stool culture for enteric pathogens

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Remission (CDAI less than 150) at 6 months starting at randomisation. The treatment phase of the study will last two years, but follow-up will be extended as long as feasible.

Secondary Outcome Measures

Name	Time	Method
1. Remission (CDAI less than 150) at 9, 12, 15, 18, 21 and 24 months following randomisation<br>2. Inflammatory Bowel Disease Questionnaire (IBDQ) and European Quality of LIfe instrument (EUROQoL) measured every three months<br>3. Number of draining fistulas at any point of evaluation<br>4. Serious adverse events caused by medication with causality assessment (World Health Organization [WHO] criteria)<br>5. Prednisone/budesonide/prednisolone free days<br>6. Number of days absent from work, school or normal daily activities due to disease related problems (should also be assessed for the month prior to randomisation)<br>7. Number and type of surgeries for Crohn's disease or related problems<br>8. Number of days in the hospital for Crohn's related problems and for any other problems<br>9. Total cost of medication, surgeries and hospitalisation during the 2 year period and possibly beyond (pharmaco-economic evaluation) and visits to specialist/general practitioner