Sepsis
Conditions
Keywords
pharmacokinetics, Cephalosporins
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.
Interventions
DRUGCefiderocol
After receipt of Cefiderocol, blood samples will be collected at various time points to determine the pharmacokinetics of Cefiderocol
Sponsors
Shionogi Inc.
Joseph L. Kuti, PharmD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cefiderocol Clearance | 8 hours | The Clearance in liters/hour of Cefiderocol from the plasma of critically ill patients receiving ECMO. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cefiderocol Area Under the Curve (AUC) | 8 hours | The AUC in milligram\*hour/liter of Cefiderocol calculated from concentrations collected between zero and 8 hours at steady-state. |
Countries
United States
Outcome results
None listed