Cefiderocol PK in Patients on ECMO

NCT04995835 | Completed Phase 1 FDA Drug

• 1 other identifier: HHC-2021-0086
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

Sepsis

Keywords

pharmacokinetics; Cephalosporins

Outcome Measures

Primary Outcomes (1)

• Cefiderocol Clearance

  The Clearance in liters/hour of Cefiderocol from the plasma of critically ill patients receiving ECMO.

  8 hours

Secondary Outcomes (1)

• Cefiderocol Area Under the Curve (AUC)

  8 hours

Study Arms (1)

Cefiderocol

EXPERIMENTAL

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

Drug: Cefiderocol

Interventions

Cefiderocol DRUG

After receipt of Cefiderocol, blood samples will be collected at various time points to determine the pharmacokinetics of Cefiderocol

Also known as: Fetroja

Cefiderocol

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joseph L. Kuti, PharmD: lead
• Shionogi Inc.: collaborator

Study Sites (2)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Columbia University/New York Presbyterian Hospital

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Sepsis

Interventions

Cefiderocol

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Joseph L Kuti, PharmD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Center for Anti-Infective Research and Development

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 9, 2021
• Study Start: July 16, 2021
• Primary Completion: June 1, 2024
• Study Completion: September 1, 2024
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)