Crohn DiseasePhase 4STOP ITNCT01817426
Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission
A Phase 4 study testing Infliximab in people with Crohn Disease, run by Copenhagen University Hospital at Herlev at 13 sites in 4 countries.
Trial summary
The purpose of this study is to determine whether infliximab can favourably and safely be discontinued in patients with Crohn's disease in sustained complete clinical, biochemical, and endoscopic remission on infliximab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Infliximab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 115 participants
- Where
- 13 sitesin 4 countries
- Study dates
- Jan 2013to May 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Luminal Crohn's disease defined according to standardized diagnostic criteria.
- Age ≥ 18 years.
- IFX induction treatment week 0, 2, 6 followed by maintenance therapy.
- IFX treatment length minimum 12 months. Episodic therapy with IFX pause > 12 weeks is not accepted within the last year. The treatment interval in the last three months has to be of 6-10 weeks.
- Complete remission defined as:
- CDAI score < 150 and
Show all 11Show fewer
- Biochemical remission, and
- No other signs of disease activity as evaluated by endoscopic examination or by magnetic resonance imaging (MRI).
- Stable remission, judged by the treating physician, at two consecutive treatments visits corresponding 2 scheduled IFX infusions. Thus, the first visit is during IFX maintaining therapy (screening visit). The second visit is at time of inclusion corresponding time of next scheduled IFX infusion (i.e. after ≈ 8 weeks).
- No use of oral steroids within 3 months prior to inclusion.
- Concomitant therapy with other immune suppressants, except steroids, is allowed. The dosage and frequency must have been stable three months prior to inclusion and must remain stable throughout the study period.
Who cannot join
- Initial indication for IFX being predominantly fistulizing perianal disease.
- Any contraindications for continuing IFX treatment, including prior acute or delayed infusion reaction to a TNF- inhibiting agent, any active infection requiring parenteral or oral antibiotic treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
- Any condition including physician finds incompatible with participation in the study or the patient being unwilling or unable to follow protocol requirements.
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
Denmark9 sites
Aarhus University Hospital
Aarhus, Aarhus C, 8000
Bispebjerg Hospital
Copenhagen, Copenhagen NV, 2400
Herlev Hospital, department of gastroenterology medical section
Herlev, 2730
Hospital enheden vest Herning
Herning
Hvidovre Hospital
Hvidovre
Nykøbing F. Sygehus
Nykøbing Falster, Nykøbing, 4800
Odense University hospital
Odense, Odense C, 5000
Silkeborg Regional Hospital, Diagnostic Center
Silkeborg
Slagelse Sygehus
Slagelse, 4200
Finland1 site
Helsinki University Hospital and University of Helsinki
Helsinki
About this study
Official title: Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission: A Multi-center, Double Blinded, Randomized, Placebo Controlled Study
The purpose of this study is to determine whether infliximab can favourably and safely be discontinued in patients with Crohn's disease in sustained complete clinical, biochemical, and endoscopic remission on infliximab.
Further to examine the clinical utility of measuring levels/activity of infliximab and activity of anti-infliximab Ab in patients in sustained complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of infliximab therapy. Additional, to investigate the optimal time-point, out of three, to measure this activity.
Read the detailed description
Recent guidelines for the management of Crohn's disease conclude that currently available data are insufficient to make firm recommendations on when and in whom to stop TNF-α antibody (TNF-α Ab) treatment after having obtained clinical remission. Further, the term "remission" is not well uniformly defined and may incorporate one or more features such as clinical remission, as assessed by CDAI, biochemical remission, endoscopical remission etc. The recently published prospective STORI study of 115 patients with luminal Crohn's disease reported that 56% of patients with Crohn's disease who had discontinued infliximab (IFX) while in clinical remission, maintained remission one year after discontinuation of therapy. Predictors of relapse included certain clinical features as well as objective biochemical and endoscopical markers of disease activity. Consistent with these data, we have recently reported that 61% of our own patients with Crohn's disease, who discontinued IFX while in complete clinical, steroid free IFX induced remission, maintained remission after one year; and half the patients were still in remission after nearly two years (median 680 days [412-948]).
A prospective randomized study of patients with Crohn's disease is necessary to confirm and extend the limited findings above, and assess whether IFX can be safely discontinued in a selected subgroup of patients with complete clinical, biochemical, and endoscopical remission.
Methods:
Study design: Prospective, double-blinded, randomized, placebo-controlled, Danish multi-center study with estimated seven Danish participating centers. Patients and treating physicians are blinded for the type of intervention.
Study population: Patients with luminal Crohn's disease in sustained complete remission on IFX.
Study treatment: Patients are randomized to either continue IFX treatment at an unchanged dosage and frequency, or alternatively to receive matching placebo. All patients will be graded for disease activity (Crohn's Disease Activity Index (CDAI), biochemical parameters, endoscopy, and/or MRI). Following screening and inclusion patients are seen after four weeks, and then every eight weeks. Endpoints are assessed at 48 weeks.
Investigators will, as explorative analyses, examine the clinical utility of measuring IFX levels and antibodies against IFX in patients with complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of IFX therapy. Additional, investigators will investigate the optimal time-point out of three to measure this activity. Patients will on the day of infusion have three blood samples drawn: one just before infusion (trough), one right after the infusion (obtained from the other arm)(peak) and one an hour after infusion (C1). Samples will be measured by common solid - and fluid phase assays for this purpose, e.g. Reporter Gene Assay (RGA).
- Conditions
- Crohn Disease
- Being tested
- Infliximab, Placebo
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| infliximab | Active comparator | Patients in this arm are randomized to continue IFX therapy at an unchanged dosage and frequency. Receives: Drug: Infliximab |
| Placebo | Placebo comparator | Patients in this arm are randomized to receive matching placebo. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to relapse after discontinuation of IFX
Relapse defined as CDAI >150 and an increase in CDAI from baseline >70 over 2 consecutive weeks (or definitive relapse as judged by treating physician)
Measured: 48 weeks
Secondary outcomes (5)
Time to loss of remission
Loss of remission defined as CDAI > 150
Measured: 48 weeks
Proportion of patients who maintain clinical remission
Defined as CDAI<150
Measured: 48 weeks
Proportion of patients who maintain clinical and endoscopic remission
Defined as CDAI<150 and SES-CD ≤ 2
Measured: 48 weeks
Proportion of patients who experience relapse (more stringent definition)
Relapse defined as CDAI >150 and an increase in CDAI from baseline >100 over 2 consecutive weeks (or definitive relapse as judged by treating physician)
Measured: 48 weeks
Proportion of patients who experience relapse
Relapse defined as CDAI >150 and an increase in CDAI from baseline >70 over 2 consecutive weeks (or definitive relapse as judged by treating physician)drug therapy.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2013 (estimated)
- Study startJan 2013
- Primary completionMay 2020
- Study completionMay 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Crohn 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital at Herlev
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Forskningsenheden, Odense University Hospital
- Investigators
- Mark Ainsworth, MD.PHD.,DMSc, Principal investigator, Herlev Hospital, dep. of gastroenterology medical section.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01817426
- Sponsor's protocol ID
- 02MA
- Acronym
- STOP IT
- Status last verified
- Mar 2022
- First submitted
- 29 Aug 2012
- Last updated
- 24 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Buhl S, Steenholdt C, Brynskov J, Christensen KR, Dorn-Rasmussen M, Thomsen OO, Bendtzen K, Klausen TW, Dahlerup JF, Thorsgaard N, Jahnsen J, Molazahi A, Pedersen N, Kjeldsen J, Almer S, Dahl EE, Vind I, Cannon AG, Marsal J, Sipponen T, Agnholt JS, Kievit HAL, Aure SL, Martinsen L, Meisner S, Hansen JM, Ainsworth MA. Discontinuation of Infliximab Therapy in Patients with Crohn's Disease. NEJM Evid. 2022 Aug;1(8):EVIDoa2200061. doi: 10.1056/EVIDoa2200061. Epub 2022 Jun 14.
PubMed 38319804Buhl SS, Steenholdt C, Brynskov J, Thomsen OO, Bendtzen K, Ainsworth MA. Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial. BMJ Open. 2014 Dec 18;4(12):e005887. doi: 10.1136/bmjopen-2014-005887.
PubMed 25524543
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission: A Multi-center, Double Blinded, Randomized, Placebo Controlled Study
- ClinicalTrials.gov ID
- NCT01817426
- Acronym / sponsor ID
- STOP IT / 02MA
- Conditions
- Crohn Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- Copenhagen University Hospital at HerlevUniversity, hospital or other
- Study start
- Jan 2013 (actual)
- Primary completion
- May 2020 (actual)
- Study completion
- May 2020 (actual)
- First posted
- 25 Mar 2013 (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 purpose of this study is to determine whether infliximab can favourably and safely be discontinued in patients with Crohn's disease in sustained complete clinical, biochemical, and endoscopic remission on infliximab.
Further to examine the clinical utility of measuring levels/activity of infliximab and activity of anti-infliximab Ab in patients in sustained complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of infliximab therapy. Additional, to investigate the optimal time-point, out of three, to measure this activity.
Detailed description
Recent guidelines for the management of Crohn's disease conclude that currently available data are insufficient to make firm recommendations on when and in whom to stop TNF-α antibody (TNF-α Ab) treatment after having obtained clinical remission. Further, the term "remission" is not well uniformly defined and may incorporate one or more features such as clinical remission, as assessed by CDAI, biochemical remission, endoscopical remission etc. The recently published prospective STORI study of 115 patients with luminal Crohn's disease reported that 56% of patients with Crohn's disease who had discontinued infliximab (IFX) while in clinical remission, maintained remission one year after discontinuation of therapy. Predictors of relapse included certain clinical features as well as objective biochemical and endoscopical markers of disease activity. Consistent with these data, we have recently reported that 61% of our own patients with Crohn's disease, who discontinued IFX while in complete clinical, steroid free IFX induced remission, maintained remission after one year; and half the patients were still in remission after nearly two years (median 680 days [412-948]).
A prospective randomized study of patients with Crohn's disease is necessary to confirm and extend the limited findings above, and assess whether IFX can be safely discontinued in a selected subgroup of patients with complete clinical, biochemical, and endoscopical remission.
Methods:
Study design: Prospective, double-blinded, randomized, placebo-controlled, Danish multi-center study with estimated seven Danish participating centers. Patients and treating physicians are blinded for the type of intervention.
Study population: Patients with luminal Crohn's disease in sustained complete remission on IFX.
Study treatment: Patients are randomized to either continue IFX treatment at an unchanged dosage and frequency, or alternatively to receive matching placebo. All patients will be graded for disease activity (Crohn's Disease Activity Index (CDAI), biochemical parameters, endoscopy, and/or MRI). Following screening and inclusion patients are seen after four weeks, and then every eight weeks. Endpoints are assessed at 48 weeks.
Investigators will, as explorative analyses, examine the clinical utility of measuring IFX levels and antibodies against IFX in patients with complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of IFX therapy. Additional, investigators will investigate the optimal time-point out of three to measure this activity. Patients will on the day of infusion have three blood samples drawn: one just before infusion (trough), one right after the infusion (obtained from the other arm)(peak) and one an hour after infusion (C1). Samples will be measured by common solid - and fluid phase assays for this purpose, e.g. Reporter Gene Assay (RGA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| infliximab | Active comparator | Drug: InfliximabPatients in this arm are randomized to continue IFX therapy at an unchanged dosage and frequency. |
| Placebo | Placebo comparator | Other: PlaceboPatients in this arm are randomized to receive matching placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Luminal Crohn's disease defined according to standardized diagnostic criteria.
- Age ≥ 18 years.
- IFX induction treatment week 0, 2, 6 followed by maintenance therapy.
- IFX treatment length minimum 12 months. Episodic therapy with IFX pause > 12 weeks is not accepted within the last year. The treatment interval in the last three months has to be of 6-10 weeks.
- Complete remission defined as:
Key exclusion criteria (3 listed)
- Initial indication for IFX being predominantly fistulizing perianal disease.
- Any contraindications for continuing IFX treatment, including prior acute or delayed infusion reaction to a TNF- inhibiting agent, any active infection requiring parenteral or oral antibiotic treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
- Any condition including physician finds incompatible with participation in the study or the patient being unwilling or unable to follow protocol requirements.
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 |
|---|---|---|
| InfliximabAlso: Remicade | Drug | infliximab |
| Placebo | Other | Placebo |
Primary outcome
Time to relapse after discontinuation of IFX
Time frame: 48 weeks
Relapse defined as CDAI >150 and an increase in CDAI from baseline >70 over 2 consecutive weeks (or definitive relapse as judged by treating physician)
5 secondary outcomes
Time to loss of remission
Time frame: 48 weeks
Proportion of patients who maintain clinical remission
Time frame: 48 weeks
Proportion of patients who maintain clinical and endoscopic remission
Time frame: 48 weeks
Proportion of patients who experience relapse (more stringent definition)
Time frame: 48 weeks
Proportion of patients who experience relapse
Time frame: 48 weeks
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 24 Mar 2022.
- Derived from this study: PubMed 38319804Buhl S, Steenholdt C, Brynskov J, Christensen KR, Dorn-Rasmussen M, Thomsen OO, Bendtzen K, Klausen TW, Dahlerup JF, Thorsgaard N, Jahnsen J, Molazahi A, Pedersen N, Kjeldsen J, Almer S, Dahl EE, Vind I, Cannon AG, Marsal J, Sipponen T, Agnholt JS, Kievit HAL, Aure SL, Martinsen L, Meisner S, Hansen JM, Ainsworth MA. Discontinuation of Infliximab Therapy in Patients with Crohn's Disease. NEJM Evid. 2022 Aug;1(8):EVIDoa2200061. doi: 10.1056/EVIDoa2200061. Epub 2022 Jun 14.
- Derived from this study: PubMed 25524543Buhl SS, Steenholdt C, Brynskov J, Thomsen OO, Bendtzen K, Ainsworth MA. Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial. BMJ Open. 2014 Dec 18;4(12):e005887. doi: 10.1136/bmjopen-2014-005887.
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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.
Mark Ainsworth, MD.PHD.,DMSc principal investigator
Herlev Hospital, dep. of gastroenterology medical section.
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Infliximab in people with Crohn Disease, run by Copenhagen University Hospital at Herlev at 13 sites in 4 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 11 inclusion and 3 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 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Denmark, Sweden, Finland, Norway. 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. Some participants in this study may receive a placebo. 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?
Time to relapse after discontinuation of IFX (time frame: 48 weeks). 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 NCT01817426, which also lists 2 linked publications.
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 24 Mar 2022.