Colitis, UlcerativePhase 4TITRATENCT03937609
TITRATE (inducTIon for acuTe ulceRATivE Colitis)
A Phase 4 study testing Infliximab in people with Colitis, Ulcerative, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 7 sites in 3 countries.
Trial summary
The aim of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by clinical and endoscopic response at week 6) as compared to the standard… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 4 Sep 2019to 15 Dec 2024
- 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
- Admission with acute severe UC (defined patients with bloody diarrhoea ≥ 6/day and any signs of systemic toxicity (pulse > 90/min, temperature > 37.8°C, haemoglobin < 105 g/l, erythrocyte sedimentation rate [ESR] > 30 mm/h, or C-reactive protein [CRP] > 30 mg/l)
- Failure to intravenous steroid treatment as defined by the Oxford criteria (more than 8 stools/d or 3-8 stools/d and CRP≥45) and a Lichtiger score ≥ 10 on day 3 after starting iv steroid treatment
- Patients going through baseline endoscopy and biopsy sampling (including CMV) before starting on IFX treatment
- In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
- The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout week 26. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
Who cannot join
- Patients at imminent need of surgery as judged by the treating clinician
- Previous use of IFX
- Enteric pathogens (such as Salmonella, Shigella, Yershinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening
- Active participation in another interventional trial
- Patients with Crohn's disease or IBD-U
- Patients with abdominal abscess
Show all 22Show fewer
- Patients with colonic stricture
- Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma, which has been removed
- Active or latent tuberculosis (screening according to national guidelines)
- Cardiac failure in NYHA stage III-IV
- History of demyelinating disease
- Recent live vaccination
- Patients with ongoing acute/chronic infection (including but not limited to HIV, hepatitis B and C) with the exception of chronic herpes labialis or cervical HPV
- History of cancer in the last 5 years with the exception of non-melanoma skin cancer
- A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures
- Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures
- Patients unable to attend all study visits
- Patients with a history of non-compliance with clinical study protocols
- Contraindication for endoscopy
- Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer
- Patients who received cyclosporine in the previous 14 days
- Pregnancy and lactation
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Netherlands3 sites
Academic Medical Center
Amsterdam
OLVG Oost
Amsterdam
Radboud UMC
Nijmegen
Norway3 sites
Klinikk Baerum Sykehus
Bærums verk
Akerhus University Hospital
Lørenskog
Helse Stavanger
Stavanger
About this study
Official title: Randomized, Multicenter Study to Investigate the Efficacy of Dashboard Driven Individualized Dosing of Infliximab Compared To Standard Dosing During the Induction in Patients With Acute Severe Ulcerative Colitis
The aim of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by clinical and endoscopic response at week 6) as compared to the standard dosing.
Read the detailed description
Previous studies performed in the AMC demonstrated that the patients with acute severe UC receiving IFX are different from patients receiving IFX while in remission.(5) The clearance of IFX is not only determined by demographic parameters (gender, body weight), blood chemistry (CRP, albumin) and anti-drug antibodies, but also disease related variables play an important role. Among others, we have demonstrated that faecal loss of IFX in ASUC patients increases IFX clearance during the induction phase (3). Furthermore, increased expression of TNF-α, the target of IFX, influences the clearance of IFX due to target mediated drug disposition (TMDD). Active IBD with high tissue concentrations of TNF-α thereby acts as a sink for anti-TNF-α antibodies (4). The PK of IFX has been mainly characterized during maintenance therapy. Evaluation of factors that influence the clearance of IFX during induction therapy will allow further optimization an individualization of IFX therapy in ASUC patients.
At present, determination of IFX concentrations in the serum with an enzyme-linked immunosorbent assay (ELISA) is time consuming; physicians often receive the results after as many as 10-20 days. To allow for proactive adjustments in dosing, faster laboratory results are required, preferably in a point-of-care setting. This test is now made available by Bühlmann Laboratories (Switzerland).
The study hypothesis is that in patients with acute severe UC an intensified and personalized IFX dosing regimen using individual PK data from point of care tests as a rapid input to the dashboard system during the induction phase will lead to improved clinical outcomes when compared to standard dosing regimen.
- Conditions
- Colitis, Ulcerative
- Being tested
- Infliximab
- Keywords
- infliximab
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade, Inflectra and Remsima
infliximab iv 5mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Standard dosing | Other | All eligible patients will receive an intravenous infusion of IFX at 5 mg/kg IFX at week 0. The control group will continue with 5 mg/kg IFX at week 2 and 6, followed by every 8 weeks. Receives: Drug: Infliximab |
| Intervention group | Experimental | All eligible patients will receive an intravenous infusion of IFX at 5 mg/kg IFX at week 0. The intervention group will receive model based dosing of infliximab with 5mg/kg at various timepoints based on the dashboard model. Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increased treatment success
Defined by clinical and endoscopic reponse. Clinical response defined as a Lichtiger score of less than 10 points with a decrease of at least 3 points compared to baseline. Endoscopic response is defined as a decrease of at least 2 points in the UCEIS at week 6 endoscopy compared to baseline
Measured: week 6
Secondary outcomes (4)
Endoscopic Remission
Mayo score 2 or less with no individual subscore less than 1
Measured: week 6 and week 26
Endoscopic Reponse
Decrease in Mayo score of 3 or more points and a 30% or more from baseline and a decrease in rectal bleeding score of 1 or more or an absolute rectal bleeding score of 0 or 1
Measured: week 6 and week 26
Clinical Remission
Measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
Measured: Week 6 and week 26
Corticosteroid-free remission
Measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
Measured: week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start4 Sep 2019
- Primary completion15 Dec 2024
- Study completion15 Dec 2024
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colitis, UlcerativeStudies 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
- Model description
- Randomized, Open-label, Multicenter Study
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Geert D'Haens, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Geert DHaens, Principal investigator, Amsterdamumc location AMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937609
- Sponsor's protocol ID
- 6746101818
- Acronym
- TITRATE
- Status last verified
- Feb 2025
- First submitted
- 30 Apr 2019
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Multicenter Study to Investigate the Efficacy of Dashboard Driven Individualized Dosing of Infliximab Compared To Standard Dosing During the Induction in Patients With Acute Severe Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT03937609
- Acronym / sponsor ID
- TITRATE / 6746101818
- Conditions
- Colitis, Ulcerative
- Keywords
- infliximab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Pfizer
- Study start
- 4 Sep 2019 (actual)
- Primary completion
- 15 Dec 2024 (actual)
- Study completion
- 15 Dec 2024 (actual)
- First posted
- 6 May 2019 (actual)
- 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 aim of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by clinical and endoscopic response at week 6) as compared to the standard dosing.
Detailed description
Previous studies performed in the AMC demonstrated that the patients with acute severe UC receiving IFX are different from patients receiving IFX while in remission.(5) The clearance of IFX is not only determined by demographic parameters (gender, body weight), blood chemistry (CRP, albumin) and anti-drug antibodies, but also disease related variables play an important role. Among others, we have demonstrated that faecal loss of IFX in ASUC patients increases IFX clearance during the induction phase (3). Furthermore, increased expression of TNF-α, the target of IFX, influences the clearance of IFX due to target mediated drug disposition (TMDD). Active IBD with high tissue concentrations of TNF-α thereby acts as a sink for anti-TNF-α antibodies (4). The PK of IFX has been mainly characterized during maintenance therapy. Evaluation of factors that influence the clearance of IFX during induction therapy will allow further optimization an individualization of IFX therapy in ASUC patients.
At present, determination of IFX concentrations in the serum with an enzyme-linked immunosorbent assay (ELISA) is time consuming; physicians often receive the results after as many as 10-20 days. To allow for proactive adjustments in dosing, faster laboratory results are required, preferably in a point-of-care setting. This test is now made available by Bühlmann Laboratories (Switzerland).
The study hypothesis is that in patients with acute severe UC an intensified and personalized IFX dosing regimen using individual PK data from point of care tests as a rapid input to the dashboard system during the induction phase will lead to improved clinical outcomes when compared to standard dosing regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, Open-label, Multicenter Study
| Arm | Type | Receives |
|---|---|---|
| Standard dosing | Other | Drug: InfliximabAll eligible patients will receive an intravenous infusion of IFX at 5 mg/kg IFX at week 0. The control group will continue with 5 mg/kg IFX at week 2 and 6, followed by every 8 weeks. |
| Intervention group | Experimental | Drug: InfliximabAll eligible patients will receive an intravenous infusion of IFX at 5 mg/kg IFX at week 0. The intervention group will receive model based dosing of infliximab with 5mg/kg at various timepoints based on the dashboard model. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Admission with acute severe UC (defined patients with bloody diarrhoea ≥ 6/day and any signs of systemic toxicity (pulse > 90/min, temperature > 37.8°C, haemoglobin < 105 g/l, erythrocyte sedimentation rate [ESR] > 30 mm/h, or C-reactive protein [CRP] > 30 mg/l)
- Failure to intravenous steroid treatment as defined by the Oxford criteria (more than 8 stools/d or 3-8 stools/d and CRP≥45) and a Lichtiger score ≥ 10 on day 3 after starting iv steroid treatment
- Patients going through baseline endoscopy and biopsy sampling (including CMV) before starting on IFX treatment
- In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
- The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
Key exclusion criteria (22 listed)
- Patients at imminent need of surgery as judged by the treating clinician
- Previous use of IFX
- Enteric pathogens (such as Salmonella, Shigella, Yershinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening
- Active participation in another interventional trial
- Patients with Crohn's disease or IBD-U
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, Inflectra and Remsimainfliximab iv 5mg/kg | Drug | Intervention group, Standard dosing |
Primary outcome
Increased treatment success
Time frame: week 6
Defined by clinical and endoscopic reponse. Clinical response defined as a Lichtiger score of less than 10 points with a decrease of at least 3 points compared to baseline. Endoscopic response is defined as a decrease of at least 2 points in the UCEIS at week 6 endoscopy compared to baseline
4 secondary outcomes
Endoscopic Remission
Time frame: week 6 and week 26
Endoscopic Reponse
Time frame: week 6 and week 26
Clinical Remission
Time frame: Week 6 and week 26
Corticosteroid-free remission
Time frame: week 26
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 6 Feb 2025.
- Individual participant dataSharing planned: No
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Colitis, Ulcerative
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 DHaens principal investigator
Amsterdamumc location AMC
7 sites in 3 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 Colitis, Ulcerative, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 7 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 6 inclusion and 22 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 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands, Norway, Ireland. 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 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?
Increased treatment success (time frame: week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2025.