TITRATE (inducTIon for acuTe ulceRATivE Colitis)

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03937609
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

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

The person who is responsible for the scientific and technical direction of the entire clinical study.

Geert DHaens
Principal Investigator Affiliation Amsterdamumc location AMC
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries Netherlands
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Colitis, Ulcerative
Additional Details

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.

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International Sites

Academic Medical Center, Amsterdam, Netherlands

Status

Recruiting

Address

Academic Medical Center

Amsterdam, ,

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