Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children

Phase 4

Not yet recruiting

• Conditions: Amoxicillin-clavulanate; Piperacillin-tazobactam; Meropenem
• Interventions: Drug: Beta-lactam antibiotic; Device: Beta-lactam model-informed precision dosing

• Registration Number: NCT06929702
• Lead Sponsor: University Hospital, Ghent

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-13
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-08
• Last Update Submitted: 2025-04-08
• Study First Posted: 2025-04-16
• Last Update Posted: 2025-04-16
• Study Start: 2025-04-22
• Primary Completion: 2027-10-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 58

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care beta-lactam treatment	Beta-lactam antibiotic	Beta-lactam standard-of-care dosing regimen, as currently used at participating wards, during 28 day study period
Beta-lactam model-informed precision dosing	Beta-lactam antibiotic	fT\>MIC-based model-informed precision dosing of beta-lactam antibiotics using a dosing calculator during 28 day study period.
Beta-lactam model-informed precision dosing	Beta-lactam model-informed precision dosing	fT\>MIC-based model-informed precision dosing of beta-lactam antibiotics using a dosing calculator during 28 day study period.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects reaching the therapeutic target 100% fT>MIC	At 48 hours after start of beta-lactam treatment	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%.

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects reaching the therapeutic target 100% fT>MIC	Within the interval 48 to 72 hours after start of beta-treatment	The therapeutic target range is 10-40 mg/L for amoxicillin, 18-72 mg/L for piperacillin and 2-8 mg/L for meropenem.
Hospital length-of-stay	From date of randomization until date of hospital discharge, with a maximum of 28 days.	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.

Trial Locations

Locations (1)

Ghent University Hospital; 🇧🇪 Ghent, Belgium