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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/18/2021.

TITRATE (inducTIon for acuTe ulceRATivE Colitis)

Clinicaltrials.gov identifier NCT03937609

Recruitment Status Recruiting

First Posted May 6, 2019

Last update posted February 6, 2020

Study Description

Brief 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 dosing.

  • Condition or Disease:Colitis, Ulcerative
  • Intervention/Treatment: Drug: Infliximab
  • Phase: Phase 4
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
  • Study Type: Interventional
  • Estimated Enrollment: 120 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Intervention Model Description: Randomized, Open-label, Multicenter Study
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • 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
  • Actual Study Start Date: September 2019
  • Estimated Primary Completion Date: December 2023
  • Estimated Study Completion Date: December 2024
Arms and interventions
Arm Intervention/treatment
Experimental: Intervention group
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.
Drug: Infliximab
infliximab iv 5mg/kg
Other: Standard dosing
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.
Drug: Infliximab
infliximab iv 5mg/kg
Outcome Measures
  • Primary Outcome Measures: 1. 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
  • Secondary Outcome Measures: 1. Endoscopic Remission [ Time Frame: week 6 and week 26 ]
    Mayo score 2 or less with no individual subscore less than 1
  • 2. Endoscopic Reponse [ Time Frame: week 6 and week 26 ]
    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
  • 3. Clinical Remission [ Time Frame: Week 6 and week 26 ]
    Measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
  • 4. Corticosteroid-free remission [ Time Frame: week 26 ]
    Measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. 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 30 mm/h, or C-reactive protein [CRP] > 30
mg/l)

2. 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

3. Patients going through baseline endoscopy and biopsy sampling (including CMV) before
starting on IFX treatment

4. In the opinion of the investigator, the subject is capable of understanding and
complying with protocol requirements.

5. The subject signs and dates a written, informed consent form and any required privacy
authorization prior to the initiation of any study procedures.

6. 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]).

Exclusion Criteria:

1. Patients at imminent need of surgery as judged by the treating clinician

2. Previous use of IFX

3. Enteric pathogens (such as Salmonella, Shigella, Yershinia, Campylobacter and C.
difficile) detected by stool analysis within 2 weeks prior to enrollment or at
screening

4. Active participation in another interventional trial

5. Patients with Crohn's disease or IBD-U

6. Patients with abdominal abscess

7. Patients with colonic stricture

8. Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma,
which has been removed

9. Active or latent tuberculosis (screening according to national guidelines)

10. Cardiac failure in NYHA stage III-IV

11. History of demyelinating disease

12. Recent live vaccination

13. 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

14. History of cancer in the last 5 years with the exception of non-melanoma skin cancer

15. A history of alcohol or illicit drug use that in the opinion of the principal
investigator (PI) would interfere with study procedures

16. Patients with psychiatric problems that in the opinion of the PI would interfere with
study procedures

17. Patients unable to attend all study visits

18. Patients with a history of non-compliance with clinical study protocols

19. Contraindication for endoscopy

20. Patients who received any investigational drug in the past 30 days or 5 half-lives,
whichever is longer

21. Patients who received cyclosporine in the previous 14 days

22. Pregnancy and lactation

Contacts and Locations
Contacts

Contact: Geert DHaens, PI 0031205663534 g.dhaens@amsterdamumc.nl

Contact: Esmé Clasquin 0031205661125 e.clasquin@amsterdamumc.nl

Locations

Netherlands
Academic Medical Center
Amsterdam

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Pfizer

Investigators

Principal Investigator: Geert DHaens Amsterdamumc location AMC

More Information
  • Responsible Party: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • ClinicalTrials.gov Identifier: NCT03937609 History of Changes
  • Other Study ID Numbers: 6746101818
  • First Posted: May 6, 2019 Key Record Dates
  • Last Update Posted: February 6, 2020
  • Last Verified: February 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Product Manufactured in and Exported from the U.S.: Yes
  • Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): infliximab
  • Additional relevant MeSH terms: Colitis, Ulcerative
    Ulcer
    Colitis