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)

NCT02581280 | Completed

• 1 other identifier: 4-2014-0919
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiac Dysfunction

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (2)

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

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

Interventions

Residual blood OTHER

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; On ECMO

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine

Seoul, 03722, South Korea

Location

Related Publications (5)

• Kim H, Jin BH, Yang S, Hahn J, Kang S, Kim D, Lee H, Kwack H, Chae SU, Bae SK, Wi J, Chang MJ. Effect of Extracorporeal Membrane Oxygenation Flow Rate on Midazolam Clearance: A Population Pharmacokinetic Study. Anesthesiology. 2026 Feb 1;144(2):485-488. doi: 10.1097/ALN.0000000000005811. Epub 2025 Nov 25. No abstract available.

  PMID: 41325279 DERIVED

• 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.

  PMID: 34937189 DERIVED

• 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.

  PMID: 32122899 DERIVED

• 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.

  PMID: 31288863 DERIVED

• 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.

  PMID: 28674057 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

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.). After ECMO device is removed, residual arterial blood samples(1\~2 mls) at each sampling time are collected and drug concentrations are assayed.

Study Officials

• Jin Wi, MD

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 20, 2015
• Study Start: December 1, 2014
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: November 13, 2019

Record last verified: 2019-11

Locations

KR (1)