Crohn's disease.
Conditions
Interventions
Randomization strategy 1:
TOP-DOWN Start infliximab 5 mg/kg three infusions at week 0, 2 and 6 + azathioprine 2 to 2.5 mg/kg day from day 0 onwards.
If patients improve and tolerate both drugs:
Con
Sponsors
Investigator Initiated Study.
Eligibility
Inclusion criteria
Inclusion criteria: 1. Men and women age 16 -75; 2. New diagnosis of Crohn’s disease, 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 / cyclosporine / FK 506 / Mycophenolate Mofetil) or biologics (Remicade or any other investigational drugs); 3. CDAI > 200 for more than four weeks (to exclude self-limited problems) in new patients or > 200 for more than two weeks for patients with known CD; 4. Symptoms do NOT improve with 5-ASA therapy in appropriate doses (Pentasa 4 grams 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
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, hematologic, 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 (< 2 years) or treatment for tuberculosis. - Less serious infections should be treated appropriately, after which the patient can be included upon the discretion of the investigator; 5. Use of biologics, corticosteroids or immunemodulators for other diseases; 6. Documented HIV infection; 7. Any currently known malignancy or premalignant lesion or any history of malignancy in the last 5 years; 8. Active pregnancy or immediate pregnancy wish; pregnancy should be deferred until at least 6 months after the last infliximab infusion. -Patient on azathioprine have to continue this medication should they become pregnant during the study; 9. Allergy to murine proteins 10. Known recent substance abuse (drugs or alcohol); 11. Symptomatic stenosis or ileal/colonic strictures with prestenotic dilatation; 12. Positive stool culture for enteric pathogens.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Remission (CDAI < 150) at 6 months starting at randomization. The treatment phase of the study will last two years, but follow-up will be extended as long as feasible. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Remission (CDAI < 150) at 9, 12, 15, 18, 21 and 24 months following randomization; 2. IBDQ and EUROQoL measured every three months; 3. Number of draining fistulas at any point of evaluation; 4. Serious adverse events caused by medication with causality assessment (WHO criteria); 5. Prednisone/Budesonide/Prednisolone free days; 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 randomization); 7. Number and type of surgeries for Crohn’s disease or related problems; 8. Number of days in the hospital for Crohn’s related problems and for any other problems; 9. Total cost of medication, surgeries and hospitalisation during the 2 year period and possibly beyond (pharmaco-economic evaluation) + visits to specialist/general practitioner. | — |
Contacts
Public ContactM.J. Spek, van der
Academic Medical Center (AMC), Department of Gastroenterology, P.O. Box 22660
Outcome results
None listed