Clinical trial NCT06929702: Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children
Official title: Early Model-Informed Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children: Big Solution for Small People?
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Amoxicillin-clavulanate
Piperacillin-tazobactam
Meropenem
Keywords: amoxicillin-clavulanate
piperacillint-tazobactam
meropenem
model-informed precision dosing
dose calculator
critically ill children
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 58
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall objective of this study is to investigate the impact of early model-informed precision dosing (MIPD) on target attainment of three beta-lactam antibiotics (amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem) in critically ill children. This evaluation includes a comparison with the more standard approach on clinical and patient-oriented measures.


Eligibility criteria: Inclusion Criteria:

* Subject aged between 0 - 17 years 10 months.
* Subject admitted to a participating ward unit (Neonatal Intensive Care Unit, Pediatric Intensive Care Unit, Pediatric Hematology-Oncology unit).
* Strongly suspected or confirmed systemic infection.
* Subject planned to start on intravenous amoxicillin-clavulanic acid, piperacillin-tazobactam or meropenem treatment at least aimed for a minimum duration of two days at time of inclusion. If the subject was previously treated with the same beta-lactam, the minimum interval to the previous beta-lactam treatment episode is
* 40 hours for amoxicillin-clavulanic acid (based on elimination half-life)
* 8 hours for piperacillin-tazobactam and meropenem (based on elimination half-life) Subject planned to start on intravenous amoxicillin (without clavulanic acid) will not be included.
* Informed consent/assent signed by parents or legal representatives of the subject.
* Not previously enrolled in this trial.

Exclusion Criteria:

* Subject with serum creatinine level ≥ 2 mg/L at inclusion.
* Subject receiving (or planned to receive) haemofiltration, extracorporeal membrane oxygenation, hemodialysis or peritoneal dialysis, molecular adsorbent recirculating system or any other exchange technique.
* Subject receiving (or planned to receive) body cooling.
* Subject death is deemed imminent and inevitable.
* Reporting of first dosing advice (based on blood sampling) is not possible within 28 hours (\*) after start treatment.
* The subject is known or suspected to be pregnant.
* The subject has a known allergy to the specific beta-lactam antibiotic.

(\*) The first (a posteriori) dose calculation and dose adjustment if necessary, is performed within a maximum timeframe of 28 hours after start of treatment (i.e. maximum timeframe to first dose adjustment).

Primary outcomes:
measure: Proportion of subjects reaching the therapeutic target 100% fT>MIC
timeFrame: At 48 hours after start of beta-lactam treatment
Secondary outcomes:
measure: Proportion of subjects reaching the therapeutic target 100% fT>MIC
timeFrame: At 120 hours after start of beta-lactam treatment
measure: Proportion of subjects reaching the therapeutic target 100% fT>MIC
timeFrame: Within the interval 48 to 72 hours after start of beta-treatment
measure: Hospital length-of-stay
timeFrame: From date of randomization until date of hospital discharge, with a maximum of 28 days.
Other outcomes:
measure: Proportion of subjects with supratherapeutic beta-lactam concentration
timeFrame: At 48 hours and at 120 hours after start of beta-lactam treatment
measure: Mean percentage of time above the therapeutic target 100% fT>MIC
timeFrame: Within the interval 0 hours (baseline) to 120 hours (Day 5) after start of beta-treatment.
measure: Proportion of subjects with clinical cure
timeFrame: At day 14 after start of beta-lactam treatment
measure: Number and type of adverse events and serious adverse events, considered to be related to study assigned dosing method (possibly, probably or definitely)
timeFrame: From start date of beta-lactam treatment until stop date of beta-lactam treatment (up to 28 days)
measure: Feasibility and compliance endpoint: time elapsed from blood collection to TDM concentration result availability
timeFrame: Blood samples taken within 120 hours of starting beta-lactam treatment (0-120 hours)
measure: Feasibility and compliance endpoint: time elapsed from first dose of antimicrobial to TDM concentration result availability
timeFrame: The first two blood samples are collected within a maximum timeframe of 24 hours after start of beta-lactam treatment. TDM concentration is measured once a day and only on weekdays.
measure: Feasibility and compliance endpoint: number of possible dose adjustments
timeFrame: At 48 hours after start of beta-lactam treatment
measure: Feasibility and compliance endpoint: Proportion of dosing advices implemented (before the next planned dose) by the prescriber
timeFrame: From start date of beta-lactam treatment until stop date of beta-lactam treatment (up to 28 days).
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: Ghent University Hospital, Princess Elisabeth Children's Hospital
name: Evelyn Dhont, Dr.
role: PRINCIPAL_INVESTIGATOR
References: