Ignite Creation Date:
2024-05-06 @ 8:19 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06338345
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-29
First Post:
2024-03-21
Brief Title:
Pharmacokinetics and Modelling of Beta-Lactam in ECMO-VA Patients
Sponsor:
University Hospital Grenoble
Organization:
University Hospital Grenoble
Study Overview
Official Title:
Pharmacokinetics and Modelling of Beta-Lactam in Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation VA-ECMO
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KAMELOT
Brief Summary:
The use of antibiotic therapy is common in intensive care units and primarily involves beta-lactams Its optimal implementation is made difficult by the pharmacokinetic changes inherent in critically ill patients
Despite the current recommendations from the French Society of Anesthesiology and Intensive Care SFAR and the French Society of Pharmacology and Therapeutics SFPT there are no recommendations on prescription modalities for patients under veno-arterial extracorporeal membrane oxygenation VA-ECMO The use of antibiotic therapy is common in VA-ECMO patients and their pharmacokinetic variability factors are then exacerbated
We aim to conduct a prospective multicenter interventional study designed to identify predictive factors for failure to achieve therapeutic target circulating concentrations of beta-lactams in patients under VA-ECMO treated with one of the studied beta-lactams
Despite the current recommendations from the French Society of Anesthesiology and Intensive Care SFAR and the French Society of Pharmacology and Therapeutics SFPT there are no recommendations on prescription modalities for patients under veno-arterial extracorporeal membrane oxygenation VA-ECMO The use of antibiotic therapy is common in VA-ECMO patients and their pharmacokinetic variability factors are then exacerbated
We aim to conduct a prospective multicenter interventional study designed to identify predictive factors for failure to achieve therapeutic target circulating concentrations of beta-lactams in patients under VA-ECMO treated with one of the studied beta-lactams
Detailed Description:
The use of antibiotic therapy is common in intensive care units and primarily involves beta-lactams Its optimal implementation is made difficult by the pharmacokinetic changes inherent in critically ill patients fluid resuscitation use of catecholamines shock state organ dysfunctions especially those involved in drug elimination implementation of extracorporeal circulations It has been demonstrated that delayed initiation of appropriate antibiotic therapy in severe infections is an independent predictor of poor prognosis
The current joint recommendations from the French Society of Anesthesiology and Intensive Care SFAR and the French Society of Pharmacology and Therapeutics SFPT formulated in 2018 have codified the implementation of beta-lactam antibiotic therapy in critically ill patients specifying administration modalities initial dosages as well as pharmacological therapeutic monitoring methods plasma monitoring of the administered molecule after 24-48 hours of administration in all patients for whom pharmacokinetic variability is expected and target plasma concentrations However there are no recommendations on prescription modalities for patients under veno-arterial extracorporeal membrane oxygenation VA-ECMO
VA-ECMO is a salvage therapy for cardio-pulmonary support via extracorporeal circulation used in severe cardiac or respiratory failures The use of antibiotic therapy is common in these patients Pharmacokinetic variability factors common to intensive care patients are then exacerbated massive fluid resuscitation haemodilution by extracorporeal circulation adsorption of xenobiotics on the exchange membrane and circuit intensity of organ failures while the severity of the patient necessitates immediate optimal antibiotic therapy administration
The literature on antibiotic pharmacokinetics in patients under VA-ECMO is scarce in the adult population Two exploratory approaches with distinct objectives can be found
A fundamental approach aiming to define the pharmacokinetic parameters apparent volume of distribution elimination half-life specific to each molecule within this population and to compare them with those observed in a reference population
A clinical approach focusing on the frequency of concentrations within the therapeutic range within the studied population proportion of patients for whom the measured plasma concentration in practice conforms to the targets formulated in the recommendations
While this second approach seems to correspond more closely to our clinical practice there are few studies in this area Bouglé et al conducted a prospective monocentric study in 2019 including all patients under ECMO-VA receiving antibiotic therapy The authors described the frequencies of plasma concentrations exceeding the lower limit of the therapeutic range Thus within this population of critically ill patients where the failure to implement optimal antibiotic therapy is likely a factor of poor prognosis 50 to 90 of patients did not reach the recommended therapeutic targets for the different beta-lactams studied Moreover the study considered overdoses as pharmacokinetic successes a highly debatable point given the complications inherent in beta-lactam overdoses However this pilot study did not focus on factors that could predict failure to achieve target concentrations
We aim to conduct a prospective multicenter interventional study designed to identify predictive factors for failure to achieve therapeutic target circulating concentrations of beta-lactams in patients under VA-ECMO treated with one of the studied beta-lactams
The current joint recommendations from the French Society of Anesthesiology and Intensive Care SFAR and the French Society of Pharmacology and Therapeutics SFPT formulated in 2018 have codified the implementation of beta-lactam antibiotic therapy in critically ill patients specifying administration modalities initial dosages as well as pharmacological therapeutic monitoring methods plasma monitoring of the administered molecule after 24-48 hours of administration in all patients for whom pharmacokinetic variability is expected and target plasma concentrations However there are no recommendations on prescription modalities for patients under veno-arterial extracorporeal membrane oxygenation VA-ECMO
VA-ECMO is a salvage therapy for cardio-pulmonary support via extracorporeal circulation used in severe cardiac or respiratory failures The use of antibiotic therapy is common in these patients Pharmacokinetic variability factors common to intensive care patients are then exacerbated massive fluid resuscitation haemodilution by extracorporeal circulation adsorption of xenobiotics on the exchange membrane and circuit intensity of organ failures while the severity of the patient necessitates immediate optimal antibiotic therapy administration
The literature on antibiotic pharmacokinetics in patients under VA-ECMO is scarce in the adult population Two exploratory approaches with distinct objectives can be found
A fundamental approach aiming to define the pharmacokinetic parameters apparent volume of distribution elimination half-life specific to each molecule within this population and to compare them with those observed in a reference population
A clinical approach focusing on the frequency of concentrations within the therapeutic range within the studied population proportion of patients for whom the measured plasma concentration in practice conforms to the targets formulated in the recommendations
While this second approach seems to correspond more closely to our clinical practice there are few studies in this area Bouglé et al conducted a prospective monocentric study in 2019 including all patients under ECMO-VA receiving antibiotic therapy The authors described the frequencies of plasma concentrations exceeding the lower limit of the therapeutic range Thus within this population of critically ill patients where the failure to implement optimal antibiotic therapy is likely a factor of poor prognosis 50 to 90 of patients did not reach the recommended therapeutic targets for the different beta-lactams studied Moreover the study considered overdoses as pharmacokinetic successes a highly debatable point given the complications inherent in beta-lactam overdoses However this pilot study did not focus on factors that could predict failure to achieve target concentrations
We aim to conduct a prospective multicenter interventional study designed to identify predictive factors for failure to achieve therapeutic target circulating concentrations of beta-lactams in patients under VA-ECMO treated with one of the studied beta-lactams
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None