Imipenem/Cilastatin/Relebactam PK in ECMO

NCT04493151 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 59752
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

beta-lactam; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Imipenem Clearance

  The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.

  6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).

• Relebactam Clearance

  The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.

  6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).

Secondary Outcomes (2)

• Imipenem Area Under the Curve (AUC)

  6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).

• Relebactam Area Under the Curve (AUC)

  6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).

Study Arms (1)

Imipenem-Cilastatin-Relebactam

EXPERIMENTAL

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

Drug: Imipenem, Cilastatin and Relebactam

Interventions

Imipenem, Cilastatin and Relebactam DRUG

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

Also known as: Recarbrio

Imipenem-Cilastatin-Relebactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joseph L. Kuti, PharmD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

MeSH Terms

Conditions

Sepsis

Interventions

imipenem, cilastatin and relebactam

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

A study limitation is the protocol defined exclusion of patients on concomitant continuous renal replacement therapy (CRRT), which is common in patients receiving ECMO (extracorporeal membrane oxygenation). Dosing modifications may be necessary in patients receiving both CRRT and ECMO.

Results Point of Contact

• Title: Dr. Joseph L. Kuti, PharmD, FIDP, FCCP
• Organization: Center for Anti-Infective Research and Development, Hartford Hospital

Joseph.Kuti@hhchealth.org

(860) 972-3612

Study Officials

• Joseph L Kuti, PharmD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Director, Center for Anti-Infective Research and Development

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 30, 2020
• Study Start: January 1, 2021
• Primary Completion: May 31, 2023
• Study Completion: June 30, 2023
• Last Updated: August 7, 2024
• Results First Posted: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)