Imipenem/Cilastatin/Relebactam PK in ECMO

NCT ID: NCT04493151

Last Updated: 2024-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2023-06-30

Brief 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.

Detailed 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.

Conditions

Sepsis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Imipenem-Cilastatin-Relebactam

Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.

Group Type: EXPERIMENTAL

Imipenem, Cilastatin and Relebactam

Intervention Type: DRUG

After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.

Interventions

Imipenem, Cilastatin and Relebactam

After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.

Intervention Type: DRUG

Other Intervention Names

Recarbrio

Eligibility Criteria

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 β-lactam agent (a history of mild rash to a β-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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Joseph L. Kuti, PharmD

OTHER

Sponsor Role: lead

Responsible Party

Joseph L. Kuti, PharmD

Associate Director, Center for Anti-Infective Research and Development

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joseph L Kuti, PharmD

Role: PRINCIPAL_INVESTIGATOR

Hartford Hospital

Locations

Hartford Hospital

Hartford, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

59752

Identifier Type: -

Identifier Source: org_study_id