Imipenem/Cilastatin/Relebactam PK in ECMO

Sepsis Clinical Trial

Official title:

Pharmacokinetics of Imipenem/Cilastatin/Relebactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04493151
• Other study ID #: 59752
• Status: Completed
• Phase: Phase 1
• Start date: January 1, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: September 2023
• Source: Hartford Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Extracorporeal membrane oxygenation (ECMO) is a from 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 re-infused 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, imipenem-cilastatin-relebactam, in critically ill patients receiving ECMO.

Description:

This is a single center, open-label study to determine imipenem-cilastatin-relebactam pharmacokinetics in critically ill patients receiving ECMO. Eight patients with suspected suspected sepsis and who are receiving ECMO will be enrolled. Each participant will receive four to six doses of imipenem-cilastatin-relebactam according to current approved prescribing information, followed by ten blood samples to determine concentrations. Non-compartmental and population pharmacokinetic analyses will be determined to assess the effects of ECMO on imipenem and relebactam pharmacokinetic parameters.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 30, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or older;

• On support with Veno-venous- or Veno-arterial-ECMO;

• Documented infection or presumed infection as confirmed by the presence of at least one of the following criteria within the past 72 hours:

• Documented fever (oral, rectal, tympanic, or core temperature > 38.5° C)

• Hypothermia (oral, rectal, tympanic, or core temperature < 35.0° C)

• An elevated white blood cell (WBC) count = 12,000 cells/mm3

Exclusion Criteria:

• If female, currently pregnant or breast feeding;

• History of any moderate or severe hypersensitivity or allergic reaction to any ß-lactam agent (a history of mild rash to a ß-lactam followed by uneventful re-exposure is not a contraindication);

• Severe renal dysfunction defined as a creatinine clearance < 15 mL/min (calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis;

• Hemoglobin less than 8 mg/dL at baseline;

• Use of probenecid, valproic acid, or imipenem within 3 days before study drug infusion;

• 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;

• Planned or prior participation in any other interventional drug study within 30 days.

Related Conditions & MeSH terms

• Sepsis

Intervention

Drug:
• Imipenem, Cilastatin and Relebactam
After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.

Locations

Country	Name	City	State
United States	Hartford Hospital	Hartford	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Joseph L. Kuti, PharmD	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Imipenem Clearance	The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.	6 hours
Primary	Relebactam Clearance	The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.	6 hours
Secondary	Imipenem Area Under the Curve (AUC)	The AUC in milligram*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state	6 hours
Secondary	Relebactam Area Under the Curve (AUC)	The AUC in milligram*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state	6 hours