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NCT Number: NCT06929702

Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children

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.

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Key information

Conditions

Amoxicillin-clavulanate Meropenem Piperacillin-tazobactam

Age range

0 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Ghent University Hospital

Ghent, 9000, Belgium

Location contact

Evelyn Dhont

PRINCIPAL_INVESTIGATOR

Pieter De Cock, Prof.

CONTACT

[email protected]

+32 9 332 29 69

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Beta-lactam antibiotic

Drug

amoxicillin-clavulanic acid, piperacillin-tazobactam, meropenem treatment

Other names: amoxicillin-clavulanic acid, piperacillin-tazobactam, meropenem

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.

Other names: Dosing calculator

Primary outcomes

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

    Time frame: 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 outcomes

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

    Time frame: At 120 hours after start of beta-lactam 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.

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

    Time frame: 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.

  3. Hospital length-of-stay

    Time frame: 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.

Other outcomes

  1. Proportion of subjects with supratherapeutic beta-lactam concentration

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

    A supratherapeutic concentration is defined as > 40 mg/L for amoxicillin, > 72 mg/L for piperacillin and > 8 mg/L for meropenem.

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

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

    Above the therapeutic target is defined as > 10 mg/L for amoxicillin, > 18 mg/L for piperacillin and > 2 mg/L for meropenem.

  3. Proportion of subjects with clinical cure

    Time frame: At day 14 after start of beta-lactam treatment

    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.

  4. 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)

  5. Feasibility and compliance endpoint: time elapsed from blood collection to TDM concentration result availability

    Time frame: Blood samples taken within 120 hours of starting beta-lactam treatment (0-120 hours)

    Blood samples will be collected within the first five days (120 hours) after starting beta-lactam treatment. A maximum of 8 blood samples will be taken from subjects in both the control and intervention group.

  6. Feasibility and compliance endpoint: time elapsed from first dose of antimicrobial to TDM concentration result availability

    Time frame: 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.

  7. Feasibility and compliance endpoint: number of possible dose adjustments

    Time frame: At 48 hours after start of beta-lactam treatment

    Number of times a dose could be adjusted based on the TDM concentration result. Three blood samples are taken within 48 hours after start of beta-lactam treatment: The first two blood samples are collected within a maximum timeframe of 24 hours after start of treatment. One random sample is taken between 24 and 48 hours after start of treatment.

  8. Feasibility and compliance endpoint: Proportion of dosing advices implemented (before the next planned dose) by the prescriber

    Time frame: From start date of beta-lactam treatment until stop date of beta-lactam treatment (up to 28 days).

Study contacts

Contact information is provided by the study sponsor or research team.

Pieter De Cock, Prof.

CONTACT

[email protected]

+32 9 332 29 69

Sponsors and collaborators

Lead sponsor

University Hospital, Ghent

Other

Registry information

Official study title

Early Model-Informed Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children: Big Solution for Small People?

Acronym: MOMENTUM

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Apr 16, 2025
Registry last updated
Apr 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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