TITRATE (inducTIon for acuTe ulceRATivE Colitis)

NCT03937609

Last updated date
Study Location
Academic Medical Center
Amsterdam, , , Netherlands
Contact
0031205663534

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Ulcerative Colitis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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 < 105 g/l, erythrocyte sedimentation rate [ESR] > 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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

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Advanced Information
Descriptive Information
Brief Title  ICMJE TITRATE (inducTIon for acuTe ulceRATivE Colitis)
Official Title  ICMJE 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
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.
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-?, the target of IFX, influences the clearance of IFX due to target mediated drug disposition (TMDD). Active IBD with high tissue concentrations of TNF-? thereby acts as a sink for anti-TNF-? 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, Open-label, Multicenter Study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colitis, Ulcerative
Intervention  ICMJE Drug: Infliximab
infliximab iv 5mg/kg
Other Name: Remicade, Inflectra and Remsima
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Infliximab
  • 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.
    Intervention: Drug: Infliximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 2, 2019)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 < 105 g/l, erythrocyte sedimentation rate [ESR] > 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Geert DHaens, PI0031205663534[email protected]
Contact: Esmé Clasquin0031205661125[email protected]
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03937609
Other Study ID Numbers  ICMJE 6746101818
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Geert D'Haens, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Sponsor  ICMJE Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Geert DHaensAmsterdamumc location AMC
PRS Account Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP