Pharmacokinetics and Modelling of Beta-Lactam in ECMO-VA Patients

NCT06338345 | Not Yet Recruiting

• 1 other identifier: 38RC23.0222
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 5

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

Conditions

Cardiogenic Shock; Post-cardiac Surgery; Cardiac Arrest; Extracorporeal Membrane Oxygenation Complication; Infections

Keywords

VA-ECMO; Infection; Beta-lactam; Pharmacokinetic; Modelling

Outcome Measures

Primary Outcomes (5)

• Predictive factors for failure to achieve target plasma concentrations in patients under VA-ECMO treated with Piperacillin-Tazobactam, Cefepime, or Meropenem.

  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.

  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.

  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.

  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.

  Plasmatic concentrations during the 24 first hours following the initiation of the antibiotherapy

  24 hour after administration

Study Arms (3)

Piperacillin Tazobactam

EXPERIMENTAL

75 patients under VA-ECMO receiving a novel administration of Piperacillin Tazobactam.

Diagnostic Test: Therapeutic drug monitoring of beta-lactam

Cefepime

EXPERIMENTAL

75 patients under VA-ECMO receiving a novel administration of Cefepime.

Diagnostic Test: Therapeutic drug monitoring of beta-lactam

Meropenem

EXPERIMENTAL

75 patients under VA-ECMO receiving a novel administration of Meropenem.

Diagnostic Test: Therapeutic drug monitoring of beta-lactam

Interventions

Therapeutic drug monitoring of beta-lactam DIAGNOSTIC_TEST

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; Meropenem; Piperacillin Tazobactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (5)

CHU de Clermont Ferrand - Hôpital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

CHU Dijon-Bourgogne

Dijon, 21000, France

Location

Aphp Pitie Salpetriere

Paris, 75013, France

Location

CHU ROUEN - Hôpital Charles-Nicolle

Rouen, 76031, France

Location

Hôpital Rangueil - CHU Toulouse

Toulouse, 31059, France

Location

Related Publications (8)

• 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.

  PMID: 12576952 BACKGROUND

• 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.

  PMID: 16625125 BACKGROUND

• 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.

  PMID: 25038549 BACKGROUND

• 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.

  PMID: 24768475 BACKGROUND

• 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.

  PMID: 23190792 BACKGROUND

• 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.

  PMID: 30831307 BACKGROUND

• 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.

  PMID: 20625153 BACKGROUND

• 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.

  PMID: 33239110 BACKGROUND

MeSH Terms

Conditions

Shock, Cardiogenic; Heart Arrest; Infections

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Study Officials

• ALEXANDRE BEHOUCHE, MD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ALEXANDRE BEHOUCHE, MD

CONTACT

04 76 76 68 79; ABehouche@chu-grenoble.fr

Anaîs ADOLLE

CONTACT

04 76 76 68 79; aadolle@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 29, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 29, 2024

Record last verified: 2024-01

Locations

FR (5)