Cefiderocol Plasma Concentrations in Patients Receiving Renal Replacement Therapy

Effect of Continuous Renal Replacement Therapy and Residual Renal Clearance on Cefiderocol Pharmacokinetics in Critically Ill Adult Patients

Continuous renal replacement therapies (CRRT) such as continuous venovenous hemofiltration are used to provide renal support for critically ill patients with acute kidney injury (AKI), particularly patients who are hemodynamically unstable. 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 CRRT 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 CRRT.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Cefiderocol

Detailed Description

This is a prospective, multi-center, open-label, Phase 1b, pharmacokinetic study of Cefiderocol in 16 critically ill patients receiving CRRT support. 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 standard of care antibiotics which may include cefiderocol as necessary to treat any current infection.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older;
2. Receiving CRRT including CVVH, CVVHD, and CVVHDF support.

Exclusion Criteria:

1. Females who are pregnant or breast-feeding;
2. 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);
3. A hemoglobin less than 8 gm/dl at baseline;
4. 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;
5. Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator);
6. 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: Basic Science
• 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 effluent rate	Drug: Cefiderocol; After receipt of Cefiderocol, blood samples will be collected at various time points to determine the pharmacokinetics of Cefiderocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cefiderocol concentration	The total and free plasma concentration of cefiderocol over time	8 to 12 hours
Cefiderocol clearance	The Clearance in liters/hour of Cefiderocol from the plasma	8 to 12 hours
Cefiderocol maximum concentration	The maximum concentration of Cefiderocol from the plasma	8 to 12 hours

Collaborators and Investigators

• Sponsor: Hartford Hospital
• Collaborators: Shionogi Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Actual): November 20, 2024
• Study Completion (Actual): November 20, 2024

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Beta Lactam Antibiotics; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Siderophores; Iron Chelating Agents; Cefiderocol
• Other Study ID Numbers: HHC-2022-0045

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