Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age0-18
SponsorUniversity Hospital, Ghent
About this trial
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
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Beta-lactam antibiotic
Drugamoxicillin-clavulanic acid, piperacillin-tazobactam, meropenem treatment
Beta-lactam model-informed precision dosing
DeviceA dosing calculator is used for the prediction of starting doses (a priori dose predictions) and follow-up doses (a posteriori calculations), using a target 100% fT\>MIC.
Treatment groups
58 Participants
are divided into 2 treatment groupsGroup A: Standard of Care beta-lactam treatmentActive comparator 1 intervention
Group B: Beta-lactam model-informed precision dosingExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of subjects reaching the therapeutic target 100% fT>MIC
fT\>MIC refers to the percentage of the dosing interval during which the beta-lactam concentration remains above the Minimum Inhibitory Concentration (MIC). A target lower boundary for trough concentrations is set to achieve 100% fT\>MIC. A conservative upper threshold for trough concentrations of 100% fT\>4xMIC is used. Therefore, the therapeutic target range is 10-40 mg/L for amoxicillin (\*), 18-72 mg/L for piperacillin (\*\*) and 2-8 mg/L for meropenem (\*\*\*). (\*) 10 mg/L for amoxicillin: taking into account a EUCAST breakpoint (for Escherichia coli infections) of 8 mg/L and a plasma protein binding of 18%. (\*\*) 18 mg/L for piperacillin: taking into account a EUCAST breakpoint (for wild-type Pseudomonas spp. infections) of 16 mg/L and a plasma protein binding of 9%. (\*\*\*) 2 mg/L for meropenem: taking into account a EUCAST breakpoint of 2 mg/L (for wild-type Enterobacterales species) and a plasma protein binding of 2%.
Time frame
At 48 hours after start of beta-lactam treatmentSecondary outcomes
1
Proportion of subjects reaching the therapeutic target 100% fT>MIC
The therapeutic target range is 10-40 mg/L for amoxicillin, 18-72 mg/L for piperacillin and 2-8 mg/L for meropenem.
Time frame
At 120 hours after start of beta-lactam treatment2
Proportion of subjects reaching the therapeutic target 100% fT>MIC
The therapeutic target range is 10-40 mg/L for amoxicillin, 18-72 mg/L for piperacillin and 2-8 mg/L for meropenem.
Time frame
Within the interval 48 to 72 hours after start of beta-treatment3
Hospital length-of-stay
Number of days from randomization to hospital discharge. Patients who are not discharged from hospital within 28 days will be censored at 28 days, the maximum follow up time. Patients who die before hospital discharge will also be censored at 28 days.
Time frame
From date of randomization until date of hospital discharge, with a maximum of 28 days.Other outcomes
1
Proportion of subjects with supratherapeutic beta-lactam concentration
A supratherapeutic concentration is defined as \> 40 mg/L for amoxicillin, \> 72 mg/L for piperacillin and \> 8 mg/L for meropenem.
Time frame
At 48 hours and at 120 hours after start of beta-lactam treatment2
Mean percentage of time above the therapeutic target 100% fT>MIC
Above the therapeutic target is defined as \> 10 mg/L for amoxicillin, \> 18 mg/L for piperacillin and \> 2 mg/L for meropenem.
Time frame
Within the interval 0 hours (baseline) to 120 hours (Day 5) after start of beta-treatment.3
Proportion of subjects with clinical cure
Clinical cure will be defined as the completion of the beta-lactam treatment course (on or prior to test-of-cure day 14) without recommencement of antibiotic therapy within 48 hours of cessation. Change of antibiotic therapy (i.e. either escalation or de-escalation) for the same indication for which the beta-lactam antibiotic was commenced is considered part of the antibiotic treatment course. Participants discharged from the hospital within 14 days after start of beta-lactam antibiotic will be considered to meet the definition of clinical cure.
Time frame
At day 14 after start of beta-lactam treatment4
Number and type of adverse events and serious adverse events, considered to be related to study assigned dosing method (possibly, probably or definitely)
Time frame
From start date of beta-lactam treatment until stop date of beta-lactam treatment (up to 28 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov