Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation (PADECMO) (PADECMO)

Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation

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

Study Overview

• Status: Recruiting
• Conditions: Pharmacokinetics; Vancomycin; Amoxicillin-clavulanate; Piperacillin-tazobactam; Teicoplanin; Meropenem; Ciprofloxacin; Amikacin; Cefazolin
• Intervention / Treatment: Other: Amoxicillin-clavulanate; Other: Piperacillin-tazobactam; Other: Meropenem; Other: Cefazolin; Other: Vancomycin; Other: Teicoplanin; Other: Ciprofloxacin; Other: Amikacin

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 Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pieter De Cock, PharmD; Phone Number: +32 9 332 29 69; Email: pieter.decock@uzgent.be

Study Locations

• Belgium
  • Brussel, Belgium, 1020
    • Recruiting
    • Queen Fabiola Children's University Hospital
    • Contact: Biarent Dominique; Email: dominique.biarent@huderf.be
    • Contact: Vens Daphne; Email: daphnevania.vens@huderf.be
  • Ghent, Belgium, 9000
    • Recruiting
    • University Hospital
    • Contact: Pieter De Cock; Email: pieter.decock@uzgent.be
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitair hospital
    • Contact: Debaveye Yves; Email: yves.debaveye@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Amoxicillin-clavulanate; Patients receiving amoxicillin-clavulanate as part of routine clinical care. Study procedure: blood sampling	Other: Amoxicillin-clavulanate; blood sampling in patients receiving amoxicillin-clavulanate as part of routine clinical care; Other Names: Blood sampling
Other: Piperacillin-tazobactam; Patients receiving piperacillin-tazobactam as part of routine clinical care. Study procedure: blood sampling	Other: Piperacillin-tazobactam; blood sampling in patients receiving piperacillin-tazobactam as part of routine clinical care.; Other Names: Blood sampling
Other: Meropenem; Patients receiving meropenem as part of routine clinical care. Study procedure: blood sampling	Other: Meropenem; blood sampling in patients receiving meropenem as part of routine clinical care.; Other Names: Blood sampling
Other: Cefazolin; Patients receiving cefazolin as part of routine clinical care. Study procedure: blood sampling	Other: Cefazolin; blood sampling in patients receiving cefazolin as part of routine clinical care.; Other Names: Blood sampling
Other: Vancomycin; Patients receiving vancomycin as part of routine clinical care. Study procedure: blood sampling	Other: Vancomycin; blood sampling in patients receiving vancomycin as part of routine clinical care.; Other Names: Blood sampling
Other: Teicoplanin; Patients receiving teicoplanin as part of routine clinical care. Study procedure: blood sampling	Other: Teicoplanin; blood sampling in patients receiving teicoplanin as part of routine clinical care.; Other Names: Blood sampling
Other: Ciprofloxacin; Patients receiving ciprofloxacin as part of routine clinical care. Study procedure: blood sampling	Other: Ciprofloxacin; blood sampling and urine sampling in patients receiving ciprofloxacin as part of routine clinical care.; Other Names: Blood sampling
Other: Amikacin; Patients receiving amikacin as part of routine clinical care. Study procedure: blood sampling	Other: Amikacin; blood sampling in patients receiving amikacin as part of routine clinical care.; Other Names: Blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	% 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	up to 1 month
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	% 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	up to 1 month
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	% 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	up to 1 month
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	% 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	up to 1 month
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	% 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	up to 1 month
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	% 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	up to 1 month
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	% 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	up to 1 month
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	% 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	up to 1 month
Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)	% of patients for whom a fAUC/MIC target>86 is achieved with the current dosing regimen off extracorporeal membrane oxygenation in steady-state conditions	up to 1 month
Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)	% 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	up to 1 month
Teicoplanin: probability of target attainment with the target being a mimimal trough concentration	% 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	up to 1 month
for teicoplanin: probability of target attainment with the target being an Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration Ratio (AUC/MIC)	% 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	up to 1 month
for amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)	% 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	up to 1 month
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration	% of patients in whom the threshold for toxicity concentration>5 mg/L is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions	up to 1 month
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration	% 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	up to 1 month
Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)	% of patients in whom a target fAUC/MIC ratio of 399 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in steady-state conditions	July 2026
Amikacin: probability of target attainment with the target being a free Area-under-the-Concentration-Time Curve over Minimal Inhibitory Concentration ratio (AUC/MIC)	% 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	July 2026

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk factors for underdosing during extracorporeal membrane oxygenation for beta-lactam antibiotics	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	up to 1 month
Risk factors for underdosing during extracorporeal membrane oxygenation for ciprofloxacin	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	up to 1 month
Risk factors for under-and overdosing during extracorporeal membrane oxygenation for vancomycin	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	up to 1 month
Risk factors for underdosing during extracorporeal membrane oxygenation for teicoplanin	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	up to 1 month
Risk factors for under-and overdosing during extracorporeal membrane oxygenation for amikacin	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	up to 1 month
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)	% 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	up to 1 month
Ciprofloxacin: probability of target attainment with the target being the free Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration ratio (fAUC/MIC)	% of patients for whom a fAUC/MIC target>86 is achieved with the current dosing regimen on extracorporeal membrane oxygenation in first-dose conditions	up to 1 month
Vancomycin: probability of target attainment with the target being the Area-under the Concentration-Time Curve over Minimal Inhibitory Concentration (AUC/MIC)	% 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	up to 1 month
Teicoplanin: probability of target attainment with the target being a mimimal trough concentration	% 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	up to 1 month
Amikacin: probability of target attainment with the target being a peak concentration over Minimal Inhibitory Concentration ratio (peak/MIC)	% 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	up to 1 month
Amikacin: probability of toxicity threshold attainment with a target being a minimal trough concentration	% 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	up to 1 month

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Annick de Jaeger, MD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2016
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: May 13, 2022
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; beta-Lactamase Inhibitors; Vancomycin; Ciprofloxacin; Amoxicillin; Cefazolin; Meropenem; Clavulanic Acid; Amoxicillin-Potassium Clavulanate Combination; Amikacin; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Teicoplanin
• Other Study ID Numbers: EC 2015/0529

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No