Top Down Versus Step Up Strategies in Crohn's Disease

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ClinicalTrials.gov Identifier: NCT00554710

Recruitment Status : Completed

First Posted : November 7, 2007

Last Update Posted : November 7, 2007

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Sponsor:

Collaborators:

Centocor BV

Schering-Plough

Information provided by:

Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Crohn's Disease	Drug: infliximab+azathioprine Drug: methylprednisolone or budesonide	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	129 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux
Study Start Date :	May 2001
Actual Study Completion Date :	January 2004

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Crohn disease

MedlinePlus related topics: Crohn's Disease

Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Azathioprine Prednisolone sodium succinate Methylprednisolone sodium succinate Budesonide Azathioprine Sodium Infliximab

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: infliximab+azathioprine infliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg Other Name: remicade/imuran
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.	Drug: methylprednisolone or budesonide methylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper Other Name: Medrol, entocort, budenofalk

Arm

Intervention/treatment

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.

Drug: infliximab+azathioprine

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

Other Name: remicade/imuran

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.

Drug: methylprednisolone or budesonide

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

Other Name: Medrol, entocort, budenofalk

Outcome Measures

Primary Outcome Measures :

remission without corticosteroids and without surgical resection [ Time Frame: month 6 and 12 after inclusion ]

Secondary Outcome Measures :

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 ]

Eligibility Criteria

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Ages Eligible for Study:	16 Years to 75 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00554710

Locations

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Belgium
Imelda GI Clinical Research Center
Bonheiden, Belgium, 2820

Sponsors and Collaborators

Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

Centocor BV

Schering-Plough

Investigators

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Principal Investigator:	Geert R DHaens, MD, PhD	Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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ClinicalTrials.gov Identifier:	NCT00554710
Other Study ID Numbers:	P01872
First Posted:	November 7, 2007 Key Record Dates
Last Update Posted:	November 7, 2007
Last Verified:	November 2007

Keywords provided by Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW:


Crohn's disease immunomodulators biologicals

Additional relevant MeSH terms:

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Crohn Disease Inflammatory Bowel Diseases Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Intestinal Diseases Methylprednisolone Budesonide Azathioprine Infliximab Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs	Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Neuroprotective Agents Protective Agents Antineoplastic Agents Bronchodilator Agents Anti-Asthmatic Agents Respiratory System Agents Dermatologic Agents Antirheumatic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic

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