Cefiderocol PK in Patients on ECMO

Phase 1

Completed

• Conditions: Sepsis
• Interventions: Drug: Cefiderocol

• Registration Number: NCT04995835
• Lead Sponsor: Joseph L. Kuti, PharmD

Brief Summary

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.

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 Timeline

• Study Start: 2021-07-16
• Study First Submitted: 2021-07-30
• Study First Submitted QC: 2021-07-30
• Study First Posted: 2021-08-09
• Primary Completion: 2024-06-01
• Study Completion: 2024-09-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cefiderocol	Cefiderocol	Participants will receive four to six doses of Cefiderocol as per current prescribing information based on calculated creatinine clearance.

Primary Outcome Measures

Name	Time	Method
Cefiderocol Clearance	8 hours	The Clearance in liters/hour of Cefiderocol from the plasma of critically ill patients receiving ECMO.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Columbia University/New York Presbyterian Hospital; 🇺🇸 New York, New York, United States