Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation (PADECMO)

Not Applicable

Recruiting

• Conditions: Meropenem; Vancomycin; Amikacin; Amoxicillin-clavulanate; Pharmacokinetics; Piperacillin-tazobactam; Cefazolin; Teicoplanin; Ciprofloxacin
• Interventions: Other: Vancomycin; Other: Cefazolin; Other: Teicoplanin; Other: Amoxicillin-clavulanate; Other: Meropenem; Other: Ciprofloxacin; Other: Amikacin; Other: Piperacillin-tazobactam

• Registration Number: NCT06426836
• Lead Sponsor: University Hospital, Ghent

Brief Summary

Pharmacokinetics of antibiotics in critically ill neonates, infants and children on extracorporeal membrane oxygenation (ECMO).

Detailed Description

The study will investigate whether - with the current dosing regimens of meropenem, piperacillin-tazobactam, amoxicillin-clavulanate, cephazolin, vancomycin, amikacin, teicoplanin and ciprofloxacin - pharmacodynamic targets are attained in a national multicentric clinical setting in pediatric patients on ECMO.

Study Timeline

• Study Start: 2016-08-19
• Study First Submitted: 2022-05-13
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-17
• Last Update Submitted: 2024-05-17
• Study First Posted: 2024-05-23
• Last Update Posted: 2024-05-23
• Primary Completion: 2025-12-01
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• patients admitted to the pediatric intensive care unit or cardiac intensive care unit
• patient age : 1,8 kg-15 years
• patient receiving antibiotic treatment (piperacillin-tazobactam, meropenem, amoxicillin-clavulanate, cephazolin, vancomycin, teicoplanin, ciprofloxacin, amikacin)
• intra-arterial or intravenous access other than the drug infusion line available for blood sampling (arterial line is preferred)
• extracorporeal membrane oxygenation circuit

Exclusion Criteria

• no catheter in place for blood sampling
• absence of parental/patient consent
• known hypersensitivity to beta-lactam antibiotics and ciprofloxacin

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vancomycin	Vancomycin	Patients receiving vancomycin as part of routine clinical care. Study procedure: blood sampling
Cefazolin	Cefazolin	Patients receiving cefazolin as part of routine clinical care. Study procedure: blood sampling
Teicoplanin	Teicoplanin	Patients receiving teicoplanin as part of routine clinical care. Study procedure: blood sampling
Amoxicillin-clavulanate	Amoxicillin-clavulanate	Patients receiving amoxicillin-clavulanate as part of routine clinical care. Study procedure: blood sampling
Meropenem	Meropenem	Patients receiving meropenem as part of routine clinical care. Study procedure: blood sampling
Ciprofloxacin	Ciprofloxacin	Patients receiving ciprofloxacin as part of routine clinical care. Study procedure: blood sampling
Amikacin	Amikacin	Patients receiving amikacin as part of routine clinical care. Study procedure: blood sampling
Piperacillin-tazobactam	Piperacillin-tazobactam	Patients receiving piperacillin-tazobactam as part of routine clinical care. Study procedure: blood sampling

Primary Outcome Measures

Name	Time	Method
Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)	up to 1 month	% of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen off extracorporeal membrane oxygenation in steady-state conditions
Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)	July 2026	% of patients in whom a target fAUC/MIC ratio of 399 is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions
Piperacillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism	up to 1 month	% of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions
Cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism	up to 1 month	% of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions
for amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)	up to 1 month	% of patients in whom a target peak/MIC ratio of 8 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions
Amoxicillin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism	up to 1 month	% of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in steady-state conditions
Meropenem: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism	up to 1 month	% of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions
Amoxicillin, piperacillin, meropenem, cefazolin: probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC) of the micro-organism	up to 1 month	% of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens before or after extracorporeal membrane oxygenation in steady-state conditions
Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)	up to 1 month	% of patients in whom a AUC/MIC target 400-600 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions
for teicoplanin: probability of target attainment with the target being an Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration Ratio (AUC/MIC)	up to 1 month	% of patients in whom an AUC/MIC of 900 is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions
Teicoplanin: probability of target attainment with the target being a mimimal trough concentration	up to 1 month	% of patients in whom a trough concentration between 20 to 30 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration	up to 1 month	% of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen before or after extracorporeal membrane oxygenation in steady-state conditions

Secondary Outcome Measures

Name	Time	Method
Risk factors for underdosing during extracorporeal membrane oxygenation for ciprofloxacin	up to 1 month	The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of ciprofloxacin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a free Area-under the concentration-Time Curve of 86
Beta-lactam antibiotics (amoxicillin, piperacillin, meropenem, cefazolin): probability of target attainment with target the % of time during which the unbound drug concentration remains above the Minimal Inhibitory Concentration (fT>MIC)	up to 1 month	% of patients for whom a target of fT\>MIC of 50% is achieved with current dosing regimens on extracorporeal membrane oxygenation in first dose conditions
Risk factors for underdosing during extracorporeal membrane oxygenation for beta-lactam antibiotics	up to 1 month	The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a percentage of time during which the unbound concentration remains above the Minimal Inhibitory Concentration (MIC) of the micro-organism of at least 50% and a maximum concentration of 10 x MIC
Teicoplanin: probability of target attainment with the target being a mimimal trough concentration	up to 1 month	% of patients in whom a trough concentration between 20 to 30 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions
Risk factors for underdosing during extracorporeal membrane oxygenation for teicoplanin	up to 1 month	The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of teicoplanin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is an Area-under the concentration-Time Curve of 900
Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)	up to 1 month	% of patients in whom a AUC/MIC target 400-600 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions
Amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)	up to 1 month	% of patients in whom a target peak/MIC ratio of 8 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions
Risk factors for under-and overdosing during extracorporeal membrane oxygenation for vancomycin	up to 1 month	The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of vancomycin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a free Area-under the concentration-Time Curve of 200 to 300
Risk factors for under-and overdosing during extracorporeal membrane oxygenation for amikacin	up to 1 month	The impact of demographic, clinical characteristics and ECMO equipment characteristics on the risk of underdosing and overdosing of amikacin will be investigated. The pharmacokinetic/pharmacodynamic target that is used is a peak over Minimal Inhibitory Concentration Ratio of 8 to 10, trough concentration below 5 mg/L and Area under the Concentration Time Curve/MIC\>399
Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)	up to 1 month	% of patients for whom a fAUC/MIC target\>86 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration	up to 1 month	% of patients in whom the threshold for toxicity concentration\>5 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions

Trial Locations

Locations (3)

University Hospital; 🇧🇪 Ghent, Belgium

Queen Fabiola Children's University Hospital; 🇧🇪 Brussel, Belgium

Universitair hospital; 🇧🇪 Leuven, Belgium