Pharmacokinetics and Modelling of Beta-Lactam in ECMO-VA Patients (KAMELOT)

March 21, 2024 updated by: University Hospital, Grenoble

Pharmacokinetics and Modelling of Beta-Lactam in Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO)

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

225

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Clermont-Ferrand, France, 63003
        • CHU de Clermont Ferrand - Hôpital Gabriel Montpied
      • Dijon, France, 21000
        • Chu Dijon-Bourgogne
        • Contact:
          • Pierre-Alain BAHR, MD
      • Paris, France, 75013
        • Aphp Pitie Salpetriere
        • Contact:
          • PAULINE DUREAU, MD
      • Rouen, France, 76031
        • CHU ROUEN - Hôpital Charles-Nicolle
        • Contact:
          • Emmanuel BESNIER, MD, PhD
      • Toulouse, France, 31059
        • Hôpital Rangueil - CHU Toulouse
        • Contact:
          • Stéphanie RUIZ, MD
        • Contact:
          • Camille MANE, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients undergoing VA-ECMO
  • Patients requiering initiation of a novel antibiotic therapy with one of the studied beta-lactam (Piperacillin-Tazobactam, Cefepime, or Meropenem) while under VA-ECMO
  • With an expected survival exceeding 24 hours
  • Patient's or their trusted person's consent

Exclusion Criteria:

  • Subject under administrative or judicial surveillance
  • Non-affiliation to social insurance
  • Pregnant or lactating patient
  • Antibiotic therapy of interest already initiated before VA-ECMO implantation
  • Contraindication to the use of beta-lactam
  • Administration modalities of beta-lactam not compliant with current recommendations
  • Subject in exclusion period from another study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Piperacillin Tazobactam
75 patients under VA-ECMO receiving a novel administration of Piperacillin Tazobactam.
Diagnostic test: Therapeutic drug monitoring of beta-lactam
During the 24 first hours after inclusion, 5 blood samples will be collected to mesure plasmatic concentrations of the studied beta-lactam, of creatinin and of albumin
Experimental: Cefepime
75 patients under VA-ECMO receiving a novel administration of Cefepime.
Diagnostic test: Therapeutic drug monitoring of beta-lactam
During the 24 first hours after inclusion, 5 blood samples will be collected to mesure plasmatic concentrations of the studied beta-lactam, of creatinin and of albumin
Experimental: Meropenem
75 patients under VA-ECMO receiving a novel administration of Meropenem.
Diagnostic test: Therapeutic drug monitoring of beta-lactam
During the 24 first hours after inclusion, 5 blood samples will be collected to mesure plasmatic concentrations of the studied beta-lactam, of creatinin and of albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive factors for failure to achieve target plasma concentrations in patients under VA-ECMO treated with Piperacillin-Tazobactam, Cefepime, or Meropenem.
Time Frame: 1 hour after administration
Plasmatic concentrations during the 24 first hours following the initiation of the antibiotherapy
1 hour after administration
Predictive factors for failure to achieve target plasma concentrations in patients under VA-ECMO treated with Piperacillin-Tazobactam, Cefepime, or Meropenem.
Time Frame: 3 hour after administration
Plasmatic concentrations during the 24 first hours following the initiation of the antibiotherapy
3 hour after administration
Predictive factors for failure to achieve target plasma concentrations in patients under VA-ECMO treated with Piperacillin-Tazobactam, Cefepime, or Meropenem.
Time Frame: 6 hour after administration
Plasmatic concentrations during the 24 first hours following the initiation of the antibiotherapy
6 hour after administration
Predictive factors for failure to achieve target plasma concentrations in patients under VA-ECMO treated with Piperacillin-Tazobactam, Cefepime, or Meropenem.
Time Frame: 12 hour after administration
Plasmatic concentrations during the 24 first hours following the initiation of the antibiotherapy
12 hour after administration
Predictive factors for failure to achieve target plasma concentrations in patients under VA-ECMO treated with Piperacillin-Tazobactam, Cefepime, or Meropenem.
Time Frame: 24 hour after administration
Plasmatic concentrations during the 24 first hours following the initiation of the antibiotherapy
24 hour after administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Investigators

  • Principal Investigator: ALEXANDRE BEHOUCHE, MD, University Hospital, Grenoble

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2024

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

March 21, 2024

First Submitted That Met QC Criteria

March 21, 2024

First Posted (Actual)

March 29, 2024

Study Record Updates

Last Update Posted (Actual)

March 29, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC23.0222

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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