Population Pharmacokinetics of Teicoplanin, Levofloxacin, Piperacillin/Tazobactam, Meropenem, Vancomycin, Remifentanil, Cefepime, Cefpirome, Sufentanil, Midazolam, Clopidogrel, Ticagrelor, Prasugrel During Veno-arterial Extracorporeal Membrane Oxygenation (VA ECMO)

Extracorporeal membrane oxygenation (ECMO) is the device which increases the supply of oxygen to the body tissues in vitro and to assist in heart and lung function. Venoarterial (VA) ECMO is used in patients with cardiogenic shock, cardiac arrest, ventricular arrhythmia and is able to secure a time to self-recovery by reducing the excessive stimulation applied to the heart. However, in ECMO patients, pharmacokinetics of drugs are changing such as increased volume of distribution (Vd) or decreased clearance (CL). For this reason, it is hard to provide the best treatment in ECMO patients. The study is to evaluate whether the PK of drugs is influenced by VA ECMO and to recommend the optimal dosing strategies for proposed drugs in adult patients receiving VA ECMO.

Study Overview

• Status: Completed
• Conditions: Cardiac Dysfunction
• Intervention / Treatment: Other: Residual blood

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients over the age of 19 who are receiving teicoplanin or levofloxacin or piperacillin/tazobactam or remifentanil or sufentanil or clopidogrel or ticagrelor while using VA ECMO in Severance Hospital, Yonsei University Health System.

Description

Inclusion Criteria:

• patient who are ≥ 19 years old and receiving VA ECMO in Severance Hospital, Yonsei University Health System.
• patient who are receiving one of these drugs: teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel
• patients who are agreed to participate in this study

Exclusion Criteria:

• patients who are pregnant
• patients who are receiving drugs that could affect study drug's concentration due to drug-drug interaction.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
On ECMO; patients who are concomitantly receiving teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel during ECMO	Other: Residual blood; Residual blood samples(1~2 cc) at each sampling time are collected from all subjects while using ECMO for drug concentration assays(LC-MS/MS etc.).
Off ECMO; patients who are concomitantly receiving teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel after removing ECMO	Other: Residual blood; Residual blood samples(1~2 cc) at each sampling time are collected from all subjects while using ECMO for drug concentration assays(LC-MS/MS etc.).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum or plasma concentration	Serum or plasma concentration of teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel	Between day0 to day3 after removing ECMO
Pharmacokinetic parameter: Cmax		Between day0 to day3 after removing ECMO
Pharmacokinetic parameter: Tmax		Between day0 to day3 after removing ECMO
Clearance		Between day0 to day3 after removing ECMO
volume of distribution		Between day0 to day3 after removing ECMO
absorption rate constant	absorption rate constant (if the drug is orally administered),	Between day0 to day3 after removing ECMO
elimination half life		Between day0 to day3 after removing ECMO
area under the curve (AUC)	area under the curve (AUC) (if possible)	Between day0 to day3 after removing ECMO

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Jin Wi, MD, Severance Hospital

Publications and helpful links

General Publications

• Hahn J, Min KL, Kang S, Yang S, Park MS, Wi J, Chang MJ. Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy. Microbiol Spectr. 2021 Dec 22;9(3):e0063321. doi: 10.1128/Spectrum.00633-21. Epub 2021 Dec 22.
• Kang S, Jang JY, Hahn J, Kim D, Lee JY, Min KL, Yang S, Wi J, Chang MJ. Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e00249-20. doi: 10.1128/AAC.00249-20. Print 2020 Apr 21.
• Hahn J, Yang S, Min KL, Kim D, Jin BH, Park C, Park MS, Wi J, Chang MJ. Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy. Crit Care. 2019 Jul 9;23(1):248. doi: 10.1186/s13054-019-2508-4.
• Wi J, Noh H, Min KL, Yang S, Jin BH, Hahn J, Bae SK, Kim J, Park MS, Choi D, Chang MJ. Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e01015-17. doi: 10.1128/AAC.01015-17. Print 2017 Sep.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: October 8, 2015
• First Submitted That Met QC Criteria: October 18, 2015
• First Posted (Estimate): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 4-2014-0919