Crohn's DiseasePhase 4NCT00554710
Top Down Versus Step Up Strategies in Crohn's Disease
A Phase 4 study testing infliximab+azathioprine and methylprednisolone or budesonide in people with Crohn's Disease, run by Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- infliximab+azathioprine and methylprednisolone or budesonide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 1 siteBelgium
- Study dates
- May 2001to Jan 2004
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- malignancy
- allergy to murine proteins
- pregnancy
- substance abuse
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux
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.
Read the 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.
- Conditions
- Crohn's Disease
- Being tested
- infliximab+azathioprine, methylprednisolone or budesonide
- Keywords
- Crohn's disease, immunomodulators, biologicals
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
infliximab+azathioprineDrug
Also called remicade/imuran
infliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg
methylprednisolone or budesonideDrug
Also called Medrol, entocort, budenofalk
methylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: methylprednisolone or budesonide |
What is being measured
The primary outcome is the main question the study is designed to answer.
remission without corticosteroids and without surgical resection
Measured: month 6 and 12 after inclusion
Secondary outcomes (5)
the time to relapse after successful induction therapy
Measured: within 24 months
the proportion of patients receiving infliximab, methylprednisolone and antimetabolites
Measured: within 24 months
the median serum C-reactive protein concentration
Measured: 24 months
the proportion of patients experiencing adverse events
Measured: 24 months
the mean endoscopic severity scores and the proportion of patients without ulcers
Measured: after 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2007 (estimated)
- Study startMay 2001
- Study completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
- Sponsor type
- University, hospital or other
- Collaborators
- Centocor BV, Schering-Plough
- Investigators
- Geert R DHaens, MD, PhD, Principal investigator, Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00554710
- Sponsor's protocol ID
- P01872
- Status last verified
- Nov 2007
- First submitted
- 6 Nov 2007
- Last updated
- 7 Nov 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18295023
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Ideal Management of Crohn's Disease: Top Down Versus Step Up Strategies. A Prospective Controlled Trial in the Benelux
- ClinicalTrials.gov ID
- NCT00554710
- Acronym / sponsor ID
- P01872
- Conditions
- Crohn's Disease
- Keywords
- Crohn's disease, immunomodulators, biologicals
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZWUniversity, hospital or other
- Collaborators
- Centocor BV, Schering-Plough
- Study start
- May 2001
- Study completion
- Jan 2004 (actual)
- First posted
- 7 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: infliximab+azathioprinePatients 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. |
| 2 | Active comparator | Drug: methylprednisolone or budesonideInduction 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. |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| infliximab+azathioprineAlso: remicade/imuraninfliximab 5 mg/kg at week 0,2 and 6 + azathioprine 2-2.5 mg/kg | Drug | 1 |
| methylprednisolone or budesonideAlso: Medrol, entocort, budenofalkmethylprednisolone 32 mg followed by taper or budesonide 9 mg/day followed by taper | Drug | 2 |
Primary outcome
remission without corticosteroids and without surgical resection
Time frame: month 6 and 12 after inclusion
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2007.
- Derived from this study: PubMed 18295023D'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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geert R DHaens, MD, PhD principal investigator
Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing infliximab+azathioprine and methylprednisolone or budesonide in people with Crohn's Disease, run by Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Nov 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
remission without corticosteroids and without surgical resection (time frame: month 6 and 12 after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00554710, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2007.