TITRATE (inducTIon for acuTe ulceRATivE Colitis)

NCT03937609 | Terminated Phase 4 DMC

• 1 other identifier: 6746101818
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 7

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.

Conditions

Colitis, Ulcerative

Keywords

infliximab

Outcome Measures

Primary Outcomes (1)

• 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

  week 6

Secondary Outcomes (4)

• Endoscopic Remission

  week 6 and week 26

• Endoscopic Reponse

  week 6 and week 26

• Clinical Remission

  Week 6 and week 26

• Corticosteroid-free remission

  week 26

Study Arms (2)

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.

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.

Drug: Infliximab

Interventions

Infliximab DRUG

infliximab iv 5mg/kg

Also known as: Remicade, Inflectra and Remsima

Intervention group; Standard dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[defined as a minimum of one year since the last menstrual period\]).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Pfizer: collaborator

Study Sites (7)

St Vincent's University Hospital

Dublin, Ireland

Location

Academic Medical Center

Amsterdam, Netherlands

Location

OLVG Oost

Amsterdam, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Klinikk Baerum Sykehus

Bærums verk, Norway

Location

Akerhus University Hospital

Lørenskog, Norway

Location

Helse Stavanger

Stavanger, Norway

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Infliximab; CT-P13

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Geert DHaens

  Amsterdamumc location AMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, Open-label, Multicenter Study

Study Record Dates

• First Submitted: April 30, 2019
• First Posted: May 6, 2019
• Study Start: September 4, 2019
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2024
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (3); IE (1); NL (3)