Crohn DiseasePhase 2NCT02247258
Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence.
A Phase 2 study testing Azathioprine, Azathioprine in case of endoscopic recurrence and Ileocolonoscopy in people with Crohn Disease and Recurrence, run by Universitaire Ziekenhuizen KU Leuven at 4 sites in 3 countries.
Trial summary
The objective of this study is to evaluate if in the prevention of postoperative recurrence of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by endoscopic criteria. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Crohn Disease, Recurrence, Azathioprine
- What is being tested?
- Azathioprine, Azathioprine in case of endoscopic recurrence and Ileocolonoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Oct 2005to May 2015
- Phase
- Phase 2
- 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
- Scheduled surgery for Crohn's disease (CD) with ileocolonic resection. Diagnosis of CD confirmed at least 4 months prior to surgery based on radiology and/or endoscopy.
- Having an increased risk for postoperative relapse for any of the following reasons: (1) active inflammatory disease with C-reactive protein level (CRP) elevated above 10 mg/L, or the use of antibiotics, steroids or biological therapy including infliximab for active ileal disease within 2 months before surgery which were administered for Crohn's disease and not for another unrelated intercurrent inflammatory or infectious disease; (2) perforating disease defined as the presence of entero-enteric or enterocutaneous fistulas or perivisceral abscess formation within 2 months before surgery. Perianal fistulizing disease will not be considered as an indication of perforating disease in the ileum or right-sided colon. (3) Previous ileo-colonic resection, (4) active smoking, (5) age below 30.
- Males and females 16-75 years old.
- Curative surgical resection. All macroscopically inflamed colonic segments (except for anorectal involvement) are to be removed at surgery. Stricturoplasties in small bowel segments not involving the anastomotic region are allowed.
- Patients able to start oral nutrition and oral therapy within 14 days from surgery.
- Patients able and willing to give written informed consent
- Women of childbearing potential should have a negative pregnancy test at inclusion.
Who cannot join
- Patients who only had strictureplasties or ileal/colonic resection without a new ileo-colonic anastomosis. Patients with ileorectal anastomosis.
- Patients with no increased risk of postoperative relapse as defined before.
- Patients with a known intolerance to azathioprine/6-mercaptopurine or with known homozygous thiopurine methyltransferase-low mutation.
- Patients in whom more than 100 cm of small bowel has been previously resected.
- Patients with active perianal disease or colorectal stenosis precluding ileocolonoscopy
- Patients with sepsis or other postoperative complications necessitating use of antibiotics for more than 14 days after surgery.
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- Patients with liver test abnormalities (serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, bilirubin > 2 ULN), leucopenia (<3000 white blood cell count /µL, <1500 neutrophils /µL), thrombopenia with < 50.000 platelets/mm3.
- Patients with severe renal, pulmonary or cardiac disease.
- Pregnant or lactating women.
- Ongoing alcohol or substance abuse.
- Ongoing or recent (within 6 months) infectious disease (viral hepatitis, tuberculosis, AIDS, Herpes zoster related disease).
- Known malignancy 5 years from surgery except for superficial epithelioma of the skin with curative resection.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
About this study
Official title: Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence: Systematic Versus Endoscopic-directed Treatment. A Multi-center, Randomized, Clinical Practice Evaluation Study.
The objective of this study is to evaluate if in the prevention of postoperative recurrence of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by endoscopic criteria. The primary endpoint, disease recurrence, encompasses symptomatic and surgical recurrence as well as severe endoscopic lesions at the final, 2 year, assessment.
- Conditions
- Crohn Disease, Recurrence, Azathioprine, Prevention
- Being tested
- Azathioprine, Azathioprine in case of endoscopic recurrence, Ileocolonoscopy, Small bowel follow trough
- Medical subject headings
- Crohn Disease, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzathioprineDrug
See arm/group descriptions
Azathioprine in case of endoscopic recurrenceDrug
See arm/group descriptions
IleocolonoscopyProcedure or surgery
See arm/group descriptions
Small bowel follow troughProcedure or surgery
See arm/group descriptions
| Study group | Role | What they receive |
|---|---|---|
| Systematic azathioprine group | Active comparator | Patients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks. Receives: Drug: Azathioprine; Procedure: Ileocolonoscopy; Procedure: Small bowel follow trough |
| Endoscopy-driven azathioprine group | Active comparator | Patients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102. Receives: Drug: Azathioprine in case of endoscopic recurrence; Procedure: Ileocolonoscopy; Procedure: Small bowel follow trough |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endoscopic remission
The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks
Measured: Week 102
Secondary outcomes (5)
Complete endoscopic remission
The percentage of patients with a Rutgeerts' score of i0 at 102 weeks
Measured: Week 102
Absence of endoscopic relapse
The percentage of patients with a Rutgeerts' score of i0-i2 at 102 weeks
Measured: Week 102
Clinical remission
The percentage of patients in clinical remission (Crohn's disease activity index, CDAI <150) at 102 weeks
Measured: Week 102
Sustained clinical remission
Crohn's disease activity index, CDAI < 150 throughout the 102 weeks study period
Measured: Week 102
Radiological remission
The percentage of patients with radiological remission at 102 weeks.
Measured: Week 102
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2014 (estimated)
- Study startOct 2005
- Primary completionApr 2014
- Study completionMay 2015
Why it stopped: Slow recruitment
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 DiseaseStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- International organization for the study of inflammatory bowel disease (IOIBD)
- Responsible party
- Sponsor
- Investigators
- Gert Van Assche, MD PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02247258
- Sponsor's protocol ID
- ML3121
- Status last verified
- Sep 2014
- First submitted
- 19 Sep 2014
- Last updated
- 29 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Ferrante M, Papamichael K, Duricova D, D'Haens G, Vermeire S, Archavlis E, Rutgeerts P, Bortlik M, Mantzaris G, Van Assche G; International Organization for Study of Inflammatory Bowel Diseases. Systematic versus Endoscopy-driven Treatment with Azathioprine to Prevent Postoperative Ileal Crohn's Disease Recurrence. J Crohns Colitis. 2015 Aug;9(8):617-24. doi: 10.1093/ecco-jcc/jjv076. Epub 2015 Apr 29.
PubMed 25926532
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azathioprine in the Prevention of Ileal Crohn's Disease Postoperative Recurrence: Systematic Versus Endoscopic-directed Treatment. A Multi-center, Randomized, Clinical Practice Evaluation Study.
- ClinicalTrials.gov ID
- NCT02247258
- Acronym / sponsor ID
- ML3121
- Conditions
- Crohn Disease, Recurrence, Azathioprine, Prevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- International organization for the study of inflammatory bowel disease (IOIBD)
- Study start
- Oct 2005
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 23 Sep 2014 (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 objective of this study is to evaluate if in the prevention of postoperative recurrence of ileal Crohn's disease immediate initiation of azathioprine postoperatively is superior to delayed (6- 12 mths.) introduction of azathioprine upon disease recurrence assessed by endoscopic criteria. The primary endpoint, disease recurrence, encompasses symptomatic and surgical recurrence as well as severe endoscopic lesions at the final, 2 year, assessment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systematic azathioprine group | Active comparator | Drug: Azathioprine, Procedure: Ileocolonoscopy, Procedure: Small bowel follow troughPatients randomized to the systematic azathioprine group received 2.0-2.5 mg/kg azathioprine within 14 days from surgery and throughout 102 weeks. |
| Endoscopy-driven azathioprine group | Active comparator | Drug: Azathioprine in case of endoscopic recurrence, Procedure: Ileocolonoscopy, Procedure: Small bowel follow troughPatients randomized to the endoscopy-driven azathioprine group received no Crohn's disease specific treatment for 26 weeks postoperatively. A first ileocolonoscopy was performed at week 26. In case of endoscopic recurrence (Rutgeerts' score i2 or higher), azathioprine was introduced at a dose of 2.0-2.5 mg/kg until week 102. If not, an ileocolonoscopy was repeated at week 52, and azathioprine started in case of endoscopic recurrence. If no endoscopic recurrence was observed, no Crohn's disease-specific treatment was given until week 102. |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Scheduled surgery for Crohn's disease (CD) with ileocolonic resection. Diagnosis of CD confirmed at least 4 months prior to surgery based on radiology and/or endoscopy.
- Having an increased risk for postoperative relapse for any of the following reasons: (1) active inflammatory disease with C-reactive protein level (CRP) elevated above 10 mg/L, or the use of antibiotics, steroids or biological therapy including infliximab for active ileal disease within 2 months before surgery which were administered for Crohn's disease and not for another unrelated intercurrent inflammatory or infectious disease; (2) perforating disease defined as the presence of entero-enteric or enterocutaneous fistulas or perivisceral abscess formation within 2 months before surgery. Perianal fistulizing disease will not be considered as an indication of perforating disease in the ileum or right-sided colon. (3) Previous ileo-colonic resection, (4) active smoking, (5) age below 30.
- Males and females 16-75 years old.
- Curative surgical resection. All macroscopically inflamed colonic segments (except for anorectal involvement) are to be removed at surgery. Stricturoplasties in small bowel segments not involving the anastomotic region are allowed.
- Patients able to start oral nutrition and oral therapy within 14 days from surgery.
Key exclusion criteria (12 listed)
- Patients who only had strictureplasties or ileal/colonic resection without a new ileo-colonic anastomosis. Patients with ileorectal anastomosis.
- Patients with no increased risk of postoperative relapse as defined before.
- Patients with a known intolerance to azathioprine/6-mercaptopurine or with known homozygous thiopurine methyltransferase-low mutation.
- Patients in whom more than 100 cm of small bowel has been previously resected.
- Patients with active perianal disease or colorectal stenosis precluding ileocolonoscopy
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 |
|---|---|---|
| AzathioprineSee arm/group descriptions | Drug | Systematic azathioprine group |
| Azathioprine in case of endoscopic recurrenceSee arm/group descriptions | Drug | Endoscopy-driven azathioprine group |
| IleocolonoscopySee arm/group descriptions | Procedure or surgery | Endoscopy-driven azathioprine group, Systematic azathioprine group |
| Small bowel follow troughSee arm/group descriptions | Procedure or surgery | Endoscopy-driven azathioprine group, Systematic azathioprine group |
Primary outcome
Endoscopic remission
Time frame: Week 102
The proportion of patients with endoscopic remission (Rutgeerts' postoperative endoscopic score i0 or i1) at 102 weeks
5 secondary outcomes
Complete endoscopic remission
Time frame: Week 102
Absence of endoscopic relapse
Time frame: Week 102
Clinical remission
Time frame: Week 102
Sustained clinical remission
Time frame: Week 102
Radiological remission
Time frame: Week 102
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2015.
- Derived from this study: PubMed 25926532Ferrante M, Papamichael K, Duricova D, D'Haens G, Vermeire S, Archavlis E, Rutgeerts P, Bortlik M, Mantzaris G, Van Assche G; International Organization for Study of Inflammatory Bowel Diseases. Systematic versus Endoscopy-driven Treatment with Azathioprine to Prevent Postoperative Ileal Crohn's Disease Recurrence. J Crohns Colitis. 2015 Aug;9(8):617-24. doi: 10.1093/ecco-jcc/jjv076. Epub 2015 Apr 29.
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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.
Gert Van Assche, MD PhD principal investigator
UZ Leuven
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azathioprine, Azathioprine in case of endoscopic recurrence and Ileocolonoscopy in people with Crohn Disease and Recurrence, run by Universitaire Ziekenhuizen KU Leuven at 4 sites in 3 countries.
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 7 inclusion and 12 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: stopped early, as of the sponsor's last update on 29 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium, Czechia, Greece. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Slow recruitment). Results are not available in the source record.
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?
Endoscopic remission (time frame: Week 102). 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 NCT02247258, 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 29 May 2015.