Inflammatory Bowel DiseasePhase 4PRECISIONNCT02453776
Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
A Phase 4 study testing PRECISION dosing Infliximab in people with Inflammatory Bowel Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Infliximab (IFX) is highly effective in inducing and maintaining remission in patients with inflammatory bowel disease (IBD). However, a large proportion of patients will eventually lose response to IFX. Therefore, strategies to improve the outcome of maintenance treatment with IFX are required. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Inflammatory Bowel Disease
- What is being tested?
- PRECISION dosing Infliximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2015to Dec 2018
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of CD or UC based on endoscopy and pathology
- 18 years or older
- Clinical remission, based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC
- Scheduled IFX maintenance treatment, regardless of interval/dosing
Who cannot join
- Dilatation or resectional surgery because of stenotic IBD in the past year
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center
Amsterdam, North Holland, 1102 AZ
About this study
Official title: Precision Dosing Versus Conventional Dosing of Infliximab Maintenance Therapy: a Randomized Controlled Multicenter Study in Patients With IBD in Clinical Remission
Infliximab (IFX) is highly effective in inducing and maintaining remission in patients with inflammatory bowel disease (IBD). However, a large proportion of patients will eventually lose response to IFX. Therefore, strategies to improve the outcome of maintenance treatment with IFX are required. Retrospective analyses suggest that adjusting IFX treatment in order to achieve IFX trough levels (TL) above a well-defined therapeutic threshold will improve the outcome of IFX treatment.
Read the detailed description
Aim of this study is to investigate the efficacy of "precision dosing" IFX maintenance treatment in comparison with standard IFX maintenance treatment in IBD patients in clinical remission.
This study will be an open, randomized, controlled trial. Inclusion criteria: Patients aged ≥18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) based on endoscopy and pathology, receiving scheduled IFX therapy for ≥14 weeks, in clinical remission based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC, respectively. Exclusion criteria: Dilatation or resectional surgury in the past year and patients with a stoma/pouch.
Patients in the intervention arm will receive individualized treatment with variable IFX dosing AND/OR intervals guided by a Bayesian pharmacokinetic model, aiming to achieve an IFX TL of 3 µg/ml. Patients in the control group will continue to receive the same IFX treatment regimen that was given prior to inclusion without dose adaptation. In the control group, treatment adjustments will only be made in case of signs of active disease, in accordance to current routine care but these patients will be considered as failures to their treatment.
Primary endpoint: Proportion of patients with sustained clinical remission (based on HBI or PM). Secondary endpoints include: annual costs of IFX treatment per patient, total annual medical costs, side effects, (sustained) biochemical remission, adverse events, quality of life, IFX trough level and IFX antibodies (with an assay allowing presence of drug).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation will result in additional blood sampling, since IFX serum concentration will be measured every 8 weeks. All other laboratory tests can be considered as routine care. Patients in the intervention group with IFX TLs >3 will receive treatment de-escalation (interval elongation and/or dose reduction) as indicated by the Baysian model. Current evidence indicates that an IFX TL of 3 suffices. Patients in the intervention group with TLs <3 will receive treatment escalation (interval shortening and/or dose increase). We hypothesize that this will result in a higher chance of remaining in clinical remission.
- Conditions
- Inflammatory Bowel Disease
- Being tested
- PRECISION dosing Infliximab
- Keywords
- Crohns Disease, Ulcerative Colitis, Infliximab, Sustained, Remission, Inflammatory bowel disease, IBD
- Medical subject headings
- Inflammatory Bowel Diseases, Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRECISION dosing InfliximabDrug
Patients in the PRECISION dosing arm will recieve model based dosing, whereas proactive adjustments in treatment can be made by measuring the Infliximab concentration.
| Study group | Role | What they receive |
|---|---|---|
| PRECISION dosing | Experimental | Infliximab may vary between 1-10 mg/kg and the interval between 4 and 12 weeks. Receives: Drug: PRECISION dosing Infliximab |
| Conventional dosing of Infliximab | No intervention | Infliximab 5 mg/kg every 8 or 6 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained clinical remission for the precision dosing group vs. the conventional IFX maintenance dosing group
Sustained clinical remission based on HBI (Crohn's disease) or PM score (Ulcerative Colitis)
Measured: 52 weeks
Secondary outcomes (4)
Cost of IFX treatment between the two groups
Comparing costs for treatment with IFX between the two groups
Measured: 52 weeks
Proportion of patients with antibodies against IFX
Measured: 52 weeks
Quality of life
With a QoL questionnaire
Measured: 52 weeks
Biochemical disease activity (CRP >5mg/L and fecal calprotectin ≥50% compared to baseline, to a value of >250 ug/g)
A rise in fecal calprotectin of ≥50% compared to baseline, to a value of >250 ug/g and/or serum CRP of >5mg/L
Measured: 26 weeks, 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study startMay 2015
- Primary completionDec 2018
- Study completionDec 2018
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 Inflammatory Bowel DiseaseStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M. Lowenberg, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- G D'Haens, Study director, Professor gastroenterology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02453776
- Sponsor's protocol ID
- 2014_354
- Acronym
- PRECISION
- Status last verified
- Aug 2019
- First submitted
- 28 Apr 2015
- Last updated
- 6 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Strik AS, Lowenberg M, Mould DR, Berends SE, Ponsioen CI, van den Brande JMH, Jansen JM, Hoekman DR, Brandse JF, Duijvestein M, Gecse KB, de Vries A, Mathot RA, D'Haens GR. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021 Feb;56(2):145-154. doi: 10.1080/00365521.2020.1856405. Epub 2020 Dec 8.
PubMed 33290108
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Dosing Versus Conventional Dosing of Infliximab Maintenance Therapy: a Randomized Controlled Multicenter Study in Patients With IBD in Clinical Remission
- ClinicalTrials.gov ID
- NCT02453776
- Acronym / sponsor ID
- PRECISION / 2014_354
- Conditions
- Inflammatory Bowel Disease
- Keywords
- Crohns Disease, Ulcerative Colitis, Infliximab, Sustained, Remission, Inflammatory bowel disease, IBD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 27 May 2015 (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.
Infliximab (IFX) is highly effective in inducing and maintaining remission in patients with inflammatory bowel disease (IBD). However, a large proportion of patients will eventually lose response to IFX. Therefore, strategies to improve the outcome of maintenance treatment with IFX are required. Retrospective analyses suggest that adjusting IFX treatment in order to achieve IFX trough levels (TL) above a well-defined therapeutic threshold will improve the outcome of IFX treatment.
Detailed description
Aim of this study is to investigate the efficacy of "precision dosing" IFX maintenance treatment in comparison with standard IFX maintenance treatment in IBD patients in clinical remission.
This study will be an open, randomized, controlled trial. Inclusion criteria: Patients aged ≥18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) based on endoscopy and pathology, receiving scheduled IFX therapy for ≥14 weeks, in clinical remission based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC, respectively. Exclusion criteria: Dilatation or resectional surgury in the past year and patients with a stoma/pouch.
Patients in the intervention arm will receive individualized treatment with variable IFX dosing AND/OR intervals guided by a Bayesian pharmacokinetic model, aiming to achieve an IFX TL of 3 µg/ml. Patients in the control group will continue to receive the same IFX treatment regimen that was given prior to inclusion without dose adaptation. In the control group, treatment adjustments will only be made in case of signs of active disease, in accordance to current routine care but these patients will be considered as failures to their treatment.
Primary endpoint: Proportion of patients with sustained clinical remission (based on HBI or PM). Secondary endpoints include: annual costs of IFX treatment per patient, total annual medical costs, side effects, (sustained) biochemical remission, adverse events, quality of life, IFX trough level and IFX antibodies (with an assay allowing presence of drug).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation will result in additional blood sampling, since IFX serum concentration will be measured every 8 weeks. All other laboratory tests can be considered as routine care. Patients in the intervention group with IFX TLs >3 will receive treatment de-escalation (interval elongation and/or dose reduction) as indicated by the Baysian model. Current evidence indicates that an IFX TL of 3 suffices. Patients in the intervention group with TLs <3 will receive treatment escalation (interval shortening and/or dose increase). We hypothesize that this will result in a higher chance of remaining in clinical remission.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PRECISION dosing | Experimental | Drug: PRECISION dosing InfliximabInfliximab may vary between 1-10 mg/kg and the interval between 4 and 12 weeks. |
| Conventional dosing of Infliximab | No intervention | –Infliximab 5 mg/kg every 8 or 6 weeks |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of CD or UC based on endoscopy and pathology
- 18 years or older
- Clinical remission, based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC
- Scheduled IFX maintenance treatment, regardless of interval/dosing
Key exclusion criteria (1 listed)
- Dilatation or resectional surgery because of stenotic IBD in the past year
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 |
|---|---|---|
| PRECISION dosing InfliximabPatients in the PRECISION dosing arm will recieve model based dosing, whereas proactive adjustments in treatment can be made by measuring the Infliximab concentration. | Drug | PRECISION dosing |
Primary outcome
Sustained clinical remission for the precision dosing group vs. the conventional IFX maintenance dosing group
Time frame: 52 weeks
Sustained clinical remission based on HBI (Crohn's disease) or PM score (Ulcerative Colitis)
4 secondary outcomes
Cost of IFX treatment between the two groups
Time frame: 52 weeks
Proportion of patients with antibodies against IFX
Time frame: 52 weeks
Quality of life
Time frame: 52 weeks
Biochemical disease activity (CRP >5mg/L and fecal calprotectin ≥50% compared to baseline, to a value of >250 ug/g)
Time frame: 26 weeks, 52 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 6 Aug 2019.
- Derived from this study: PubMed 33290108Strik AS, Lowenberg M, Mould DR, Berends SE, Ponsioen CI, van den Brande JMH, Jansen JM, Hoekman DR, Brandse JF, Duijvestein M, Gecse KB, de Vries A, Mathot RA, D'Haens GR. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021 Feb;56(2):145-154. doi: 10.1080/00365521.2020.1856405. Epub 2020 Dec 8.
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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.
G D'Haens study director
Professor gastroenterology
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 PRECISION dosing Infliximab in people with Inflammatory Bowel Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 1 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 6 Aug 2019. 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 Netherlands. 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?
Sustained clinical remission for the precision dosing group vs. the conventional IFX maintenance dosing group (time frame: 52 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 NCT02453776, 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 6 Aug 2019.