Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation (PADECMO)

Pharmacokinetics Clinical Trial

— PADECMO  

Official title:

Pediatric Antibiotic Dosing in Extracorporal Membrane Oxygenation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06426836
• Other study ID #: EC 2015/0529
• Status: Recruiting
• Phase: N/A
• Start date: August 19, 2016
• Est. completion date: July 1, 2026

Study information

• Verified date: May 2024
• Source: University Hospital, Ghent
• Contact: Pieter De Cock, PharmD
• Phone: +32 9 332 29 69
• Email: pieter.decock[@]uzgent.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: July 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Amikacin
• Amoxicillin-clavulanate
• Cefazolin
• Ciprofloxacin
• Meropenem
• Pharmacokinetics
• Piperacillin-tazobactam
• Teicoplanin
• Vancomycin

Intervention

Other:
• Amoxicillin-clavulanate
blood sampling in patients receiving amoxicillin-clavulanate as part of routine clinical care
• Piperacillin-tazobactam
blood sampling in patients receiving piperacillin-tazobactam as part of routine clinical care.
• Meropenem
blood sampling in patients receiving meropenem as part of routine clinical care.
• Cefazolin
blood sampling in patients receiving cefazolin as part of routine clinical care.
• Vancomycin
blood sampling in patients receiving vancomycin as part of routine clinical care.
• Teicoplanin
blood sampling in patients receiving teicoplanin as part of routine clinical care.
• Ciprofloxacin
blood sampling and urine sampling in patients receiving ciprofloxacin as part of routine clinical care.
• Amikacin
blood sampling in patients receiving amikacin as part of routine clinical care.

Locations

Country	Name	City	State
Belgium	Queen Fabiola Children's University Hospital	Brussel
Belgium	University Hospital	Ghent
Belgium	Universitair hospital	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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