Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children

NCT06929702 | Not Yet Recruiting Phase 4

• 2 other identifiers: ONZ-2024-02952024-516447-12-00
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Amoxicillin-clavulanate; Piperacillin-tazobactam; Meropenem

Keywords

amoxicillin-clavulanate; piperacillint-tazobactam; meropenem; model-informed precision dosing; dose calculator; critically ill children

Outcome Measures

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%.

  At 48 hours after start of beta-lactam treatment

Secondary Outcomes (3)

• Proportion of subjects reaching the therapeutic target 100% fT>MIC

  At 120 hours after start of beta-lactam treatment

• Proportion of subjects reaching the therapeutic target 100% fT>MIC

  Within the interval 48 to 72 hours after start of beta-treatment

• Hospital length-of-stay

  From date of randomization until date of hospital discharge, with a maximum of 28 days.

Other Outcomes (8)

• Proportion of subjects with supratherapeutic beta-lactam concentration

  At 48 hours and at 120 hours after start of beta-lactam treatment

• Mean percentage of time above the therapeutic target 100% fT>MIC

  Within the interval 0 hours (baseline) to 120 hours (Day 5) after start of beta-treatment.

• Proportion of subjects with clinical cure

  At day 14 after start of beta-lactam treatment

Study Arms (2)

Standard of Care beta-lactam treatment

ACTIVE COMPARATOR

Beta-lactam standard-of-care dosing regimen, as currently used at participating wards, during 28 day study period

Drug: Beta-lactam antibiotic

Beta-lactam model-informed precision dosing

EXPERIMENTAL

fT\>MIC-based model-informed precision dosing of beta-lactam antibiotics using a dosing calculator during 28 day study period.

Drug: Beta-lactam antibiotic; Device: Beta-lactam model-informed precision dosing

Interventions

Beta-lactam antibiotic DRUG

amoxicillin-clavulanic acid, piperacillin-tazobactam, meropenem treatment

Also known as: amoxicillin-clavulanic acid, piperacillin-tazobactam, meropenem

Beta-lactam model-informed precision dosing; Standard of Care beta-lactam treatment

Beta-lactam model-informed precision dosing DEVICE

A 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.

Also known as: Dosing calculator

Beta-lactam model-informed precision dosing

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• hours for amoxicillin-clavulanic acid (based on elimination half-life)
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

MeSH Terms

Interventions

Monobactams; Amoxicillin-Potassium Clavulanate Combination; Piperacillin, Tazobactam Drug Combination; Meropenem

Intervention Hierarchy (Ancestors)

beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Drug Combinations; Pharmaceutical Preparations; Tazobactam; Penicillanic Acid; Piperacillin; Sulfones; Thienamycins; Carbapenems

Study Officials

• Evelyn Dhont, Dr.

  Ghent University Hospital, Princess Elisabeth Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pieter De Cock, Prof.

CONTACT

+32 9 332 29 69; pieter.decock@uzgent.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and legal representatives are blinded for the allocation to the intervention or standard-of-care arm until the end of study. The statistician is kept blinded until after data analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: April 16, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 16, 2025

Record last verified: 2025-04

Locations

BE (1)