Cefiderocol PK in Patients on ECMO

Ex Vivo Sequestration and Pharmacokinetics of Cefiderocol in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life-support for critically ill patients where blood is extracted from the vascular system and circulated by a mechanical pump while it is oxygenated and reinfused into the patient's circulation. It is well known that critically ill patients may experience alterations in antibiotic pharmacokinetics, and as a result, dosing modifications are generally required. There is a need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs. This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic, Cefiderocol, in critically ill patient receiving ECMO.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Drug: Cefiderocol

Detailed Description

This is a prospective, open-label, Phase 1b, pharmacokinetic study of Cefiderocol in 8 critically ill patients receiving ECMO support at Hartford Hospital. Informed consent will be collected from all study participants, legal authorized representative, or their next of kin in order to participate. This is not a treatment study; all participants will receive other antibiotics as necessary to treat any current infection.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joseph L Kuti, PharmD; Phone Number: 8609723612; Email: joseph.kuti@hhchealth.org
• Study Contact Backup: Name: Elizabeth Cyr; Phone Number: 8609729290; Email: Elizabeth.Cyr@hhchealth.org

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Recruiting
      • Hartford Hospital
      • Contact: Joseph L Kuti, PharmD; Phone Number: 860-972-3612; Email: joseph.kuti@hhchealth.org
      • Sub-Investigator: Jason A Gluck, DO
      • Sub-Investigator: David P Nicolau, PharmD
      • Sub-Investigator: Tomefa E Asempa, PharmD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University/New York Presbyterian Hospital
      • Contact: Amy Dzierba, PharmD; Email: ald9012@nyp.org
      • Principal Investigator: Daryl Abrams, MD
      • Sub-Investigator: Amy Dzierba, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older
• On support with veno-venous- or veno-arterial-ECMO

Exclusion Criteria:

• Females who are pregnant or breast-feeding
• History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (a history of mild rash to a cephalosporin followed by uneventful re-exposure is not a contraindication)
• Receiving Cefiderocol to treat documented or suspected infection within 72 hours of screening, or expected to receive Cefiderocol during the study intervention phase
• Severe renal dysfunction defined as a CrCL < 15 mL/min (as calculated by the Cockcroft Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis
• A hemoglobin less than 7.2 gm/dl at baseline
• Acute liver injury, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal, or AST or ALT > 3 times the upper limit of normal with an associated total bilirubin > 2 times upper limit of normal
• Any rapidly progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator)
• Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefiderocol; Participants will receive four to six doses of Cefiderocol as per current prescribing information based on calculated creatinine clearance.	Drug: Cefiderocol; After receipt of Cefiderocol, blood samples will be collected at various time points to determine the pharmacokinetics of Cefiderocol; Other Names: Fetroja

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cefiderocol Clearance	The Clearance in liters/hour of Cefiderocol from the plasma of critically ill patients receiving ECMO.	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cefiderocol Area Under the Curve (AUC)	The AUC in milligram*hour/liter of Cefiderocol calculated from concentrations collected between zero and 8 hours at steady-state.	8 hours

Collaborators and Investigators

• Sponsor: Joseph L. Kuti, PharmD
• Collaborators: Shionogi Inc.
• Investigators: Principal Investigator: Joseph L Kuti, PharmD, Hartford Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2021
• Primary Completion (Estimated): July 16, 2024
• Study Completion (Estimated): July 16, 2024

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: pharmacokinetics; Cephalosporins
• Other Study ID Numbers: HHC-2021-0086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes