Sepsis
Conditions
Keywords
pharmacokinetics, echinocandins
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 echinocandin, Rezafungin, in critically ill patients receiving ECMO
Detailed description
This is a prospective, open-label, Phase 1b, pharmacokinetic study of Rezafungin 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
DRUGRezafungin
After receipt of Rezafungin, blood samples will be collected at various time points to determine the pharmacokinetics of Rezafungin.
Sponsors
Melinta Therapeutics, LLC
Hartford Hospital
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
* 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 * Receiving or likely to require intermittent 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rezafungin Clearance | 168 hours | The Clearance in liters/hour of Rezafungin from the plasma of critically ill patients receiving ECMO |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rezafungin Area Under the Curve (AUC) | 168 hours | The AUC in milligram\*hour/liter of Rezafungin calculated from concentrations collected between zero and 168 hours at steady-state. |
Outcome results
None listed