TITRATE (inducTIon for acuTe ulceRATivE Colitis)

NCT ID: NCT03937609

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-04
• Study Completion Date: 2024-12-15

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-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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Infliximab

Intervention Type: DRUG

infliximab iv 5mg/kg

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.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

infliximab iv 5mg/kg

Interventions

Infliximab

infliximab iv 5mg/kg

Intervention Type: DRUG

Other Intervention Names

Remicade, Inflectra and Remsima

Eligibility 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 < 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

Geert D'Haens

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Geert DHaens

Role: PRINCIPAL_INVESTIGATOR

Amsterdamumc location AMC

Locations

St Vincent's University Hospital

Dublin, , Ireland

Academic Medical Center

Amsterdam, , Netherlands

OLVG Oost

Amsterdam, , Netherlands

Radboud UMC

Nijmegen, , Netherlands

Klinikk Baerum Sykehus

Bærums verk, , Norway

Akerhus University Hospital

Lørenskog, , Norway

Helse Stavanger

Stavanger, , Norway

Countries

Ireland; Netherlands; Norway

Other Identifiers

6746101818

Identifier Type: -

Identifier Source: org_study_id