Top Down Versus Step Up Strategies in Crohn's Disease - Full Text View

Sponsors and Collaborators:	Belgian IBD Research Group Centocor BV Schering-Plough
Information provided by:	Belgian IBD Research Group
ClinicalTrials.gov Identifier:	NCT00554710

Purpose

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	Intervention	Phase
Crohn's Disease	Drug: infliximab+azathioprine Drug: methylprednisolone or budesonide	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux

Resource links provided by NLM:

Further study details as provided by Belgian IBD Research Group:

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 ]

Enrollment:	129
Study Start Date:	May 2001
Study Completion Date:	January 2004

Arms	Assigned Interventions
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 infliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg
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 methylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper

Arms

Assigned Interventions

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

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

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

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

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

Ages Eligible for Study:	16 Years to 75 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554710

Locations

Belgium
Imelda GI Clinical Research Center
Bonheiden, Belgium, 2820

Sponsors and Collaborators

Belgian IBD Research Group

Centocor BV

Schering-Plough

Investigators

Principal Investigator:

Geert R DHaens, MD, PhD

Belgian IBD Research Group

More Information

No publications provided by Belgian IBD Research Group

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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 JC, van der Woude J, Ochsenkühn 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):660-7.

Study ID Numbers:	P01872
Study First Received:	November 6, 2007
Last Updated:	November 6, 2007
ClinicalTrials.gov Identifier:	NCT00554710 History of Changes
Health Authority:	Belgium: Institutional Review Board

Keywords provided by Belgian IBD Research Group:

Crohn's disease
immunomodulators
biologicals

Study placed in the following topic categories:

Antimetabolites
Anti-Inflammatory Agents
Crohn's Disease
Immunologic Factors
Infliximab
Gastrointestinal Diseases
Methylprednisolone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Inflammatory Bowel Diseases
Antiemetics
Prednisolone acetate
Hormones
Neuroprotective Agents
Ileal Diseases

Azathioprine
Methylprednisolone Hemisuccinate
Antineoplastic Agents, Hormonal
Ileitis
Enteritis
Budesonide
Anti-Asthmatic Agents
Methylprednisolone acetate
Intestinal Diseases
Glucocorticoids
Immunosuppressive Agents
Digestive System Diseases
Crohn Disease
Prednisolone
Peripheral Nervous System Agents

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Respiratory System Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Infliximab
Gastrointestinal Diseases
Methylprednisolone
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Inflammatory Bowel Diseases
Prednisolone acetate

Hormones
Neuroprotective Agents
Ileal Diseases
Azathioprine
Therapeutic Uses
Dermatologic Agents
Methylprednisolone Hemisuccinate
Antineoplastic Agents, Hormonal
Ileitis
Enteritis
Gastrointestinal Agents
Budesonide
Anti-Asthmatic Agents
Methylprednisolone acetate
Intestinal Diseases

ClinicalTrials.gov processed this record on July 02, 2009