Cefiderocol PK in Patients on ECMO

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Cefiderocol


Participation Criteria
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Eligibility Criteria
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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 8 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, Cephalosporins