Rezafungin PK in Patients on ECMO

Pharmacokinetics and Ex Vivo Sequestration of Rezafungin 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 echinocandin, Rezafungin, in critically ill patients receiving ECMO

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Drug: Rezafungin

Detailed Description

This is a prospective, open-label, Phase 1b, pharmacokinetic study of Rezafunginin 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: 860-972-3612; Email: joseph.kuti@hhchealth.org
• Study Contact Backup: Name: Keelyn Kotecki; Phone Number: 860-972-3004; Email: keelyn.kotecki@hhchealth.org

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• Receiving venovenous or venoarterial ECMO support.

Exclusion Criteria:

• Females who are pregnant or breast-feeding
• History of any moderate or severe hypersensitivity or allergic reaction to any echinocandin antifungal
• Receiving rezafungin to treat documented or suspected infection within 14 days of screening, or expected to receive rezafungin 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
• Patients expected to have ECMO discontinued within the next 24 hours
• 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: Rezafungin; Participants will receive one dose of rezafungin as per current prescribing information.	Drug: Rezafungin; After receipt of Rezafungin, blood samples will be collected at various time points to determine the pharmacokinetics of Rezafungin.; Other Names: rezafungin acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rezafungin Clearance	The Clearance in liters/hour of Rezafungin from the plasma of critically ill patients receiving ECMO	168 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rezafungin Area Under the Curve (AUC)	The AUC in milligram*hour/liter of Rezafungin calculated from concentrations collected between zero and 168 hours at steady-state.	168 hours

Collaborators and Investigators

• Sponsor: Hartford Hospital
• Collaborators: Melinta Therapeutics, LLC
• Investigators: Principal Investigator: Joseph L. Kuti, PharmD, Hartford Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: pharmacokinetics; echinocandins
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Rezafungin
• Other Study ID Numbers: HHC-2024-0064

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No