Pharmacokinetics and Modelling of Beta-Lactam in ECMO-VA Patients
NCT ID: NCT06338345
Last Updated: 2024-03-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
NOT_YET_RECRUITING
NA
225 participants
INTERVENTIONAL
2024-09-01
2028-09-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Piperacillin Tazobactam
75 patients under VA-ECMO receiving a novel administration of Piperacillin Tazobactam.
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
Cefepime
75 patients under VA-ECMO receiving a novel administration of Cefepime.
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
Meropenem
75 patients under VA-ECMO receiving a novel administration of Meropenem.
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
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University Hospital, Grenoble
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
ALEXANDRE BEHOUCHE, MD
Role: PRINCIPAL_INVESTIGATOR
University Hospital, Grenoble
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
CHU de Clermont Ferrand - Hôpital Gabriel Montpied
Clermont-Ferrand, , France
CHU Dijon-Bourgogne
Dijon, , France
Aphp Pitie Salpetriere
Paris, , France
CHU ROUEN - Hôpital Charles-Nicolle
Rouen, , France
Hôpital Rangueil - CHU Toulouse
Toulouse, , France
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Pierre-Alain BAHR, MD
Role: primary
PAULINE DUREAU, MD
Role: primary
Emmanuel BESNIER, MD, PhD
Role: primary
Stéphanie RUIZ, MD
Role: primary
Camille MANE, MD
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Leone M, Bourgoin A, Cambon S, Dubuc M, Albanese J, Martin C. Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med. 2003 Feb;31(2):462-7. doi: 10.1097/01.CCM.0000050298.59549.4A.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient--concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev. 2014 Nov 20;77:3-11. doi: 10.1016/j.addr.2014.07.006. Epub 2014 Jul 15.
Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, Hope WW, Farkas A, Neely MN, Schentag JJ, Drusano G, Frey OR, Theuretzbacher U, Kuti JL; International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014 Jun;14(6):498-509. doi: 10.1016/S1473-3099(14)70036-2. Epub 2014 Apr 24.
Shekar K, Roberts JA, Welch S, Buscher H, Rudham S, Burrows F, Ghassabian S, Wallis SC, Levkovich B, Pellegrino V, McGuinness S, Parke R, Gilder E, Barnett AG, Walsham J, Mullany DV, Fung YL, Smith MT, Fraser JF. ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO. BMC Anesthesiol. 2012 Nov 28;12:29. doi: 10.1186/1471-2253-12-29.
Bougle A, Dujardin O, Lepere V, Ait Hamou N, Vidal C, Lebreton G, Salem JE, El-Helali N, Petijean G, Amour J. PHARMECMO: Therapeutic drug monitoring and adequacy of current dosing regimens of antibiotics in patients on Extracorporeal Life Support. Anaesth Crit Care Pain Med. 2019 Oct;38(5):493-497. doi: 10.1016/j.accpm.2019.02.015. Epub 2019 Mar 1.
Lamoth F, Buclin T, Pascual A, Vora S, Bolay S, Decosterd LA, Calandra T, Marchetti O. High cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients with mild impairment of renal function. Antimicrob Agents Chemother. 2010 Oct;54(10):4360-7. doi: 10.1128/AAC.01595-08. Epub 2010 Jul 12.
Kuhn D, Metz C, Seiler F, Wehrfritz H, Roth S, Alqudrah M, Becker A, Bracht H, Wagenpfeil S, Hoffmann M, Bals R, Hubner U, Geisel J, Lepper PM, Becker SL. Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study. Crit Care. 2020 Nov 25;24(1):664. doi: 10.1186/s13054-020-03397-1.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
38RC23.0222
Identifier Type: -
Identifier Source: org_study_id