Clinical trial NCT04995835: Cefiderocol PK in Patients on ECMO
Official title: Ex Vivo Sequestration and Pharmacokinetics of Cefiderocol in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sepsis
Keywords: pharmacokinetics
Cephalosporins
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Shionogi Inc.
First posted: 2021-08-09
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cefiderocol Clearance
timeFrame: 8 hours
Secondary outcomes:
measure: Cefiderocol Area Under the Curve (AUC)
timeFrame: 8 hours
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New York
country: United States
facility: Columbia University/New York Presbyterian Hospital
state: New York
Study officials:
affiliation: Hartford Hospital
name: Joseph L Kuti, PharmD
role: PRINCIPAL_INVESTIGATOR
References: