PK/PD Study of Anti-Infective Drugs in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation Treatment (ECMO)

PK/PD Study of Antibiotics in Critically Ill Patients Receiving ECMO

Extracorporeal membrane pulmonary oxygenation (ECMO) may provide partial or complete support for organ replacement in patients with severe cardiopulmonary failure, buying time for further management of the primary disease. However, ECMO may significantly alter the pharmacokinetic and pharmacodynamic profiles of critically ill patients, affecting the safety and efficacy of drug therapy. This prospective observational study aims to investigate the impact of ECMO treatment on the pharmacokinetics and pharmacodynamics of antimicrobial drugs in critically ill adult patients. Investigators intend to establish a Population Pharmacokinetic (POP PK) and Pharmacokinetic/Pharmacodynamic (PK/PD) model by prospectively collecting blood samples from patients and relevant treatment data. The primary objective is to quantitatively characterize the pharmacokinetic profiles of critically ill patients undergoing ECMO support and provide model-based recommendations for drug regimens tailored to critically ill patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Illness; Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Device: ECMO treatment

Detailed Description

Extracorporeal Membrane Pulmonary Oxygenation (ECMO) is a temporary life-support system used to provide partial or complete organ support for adult patients with severe cardiopulmonary failure. ECMO stabilizes the vital signs of critically ill patients, allowing time for further management of the underlying disease. Effective pharmacologic treatment of the primary condition is crucial for successful patient outcomes.

Critically ill patients often exhibit significant variability in pharmacokinetics (PK) compared to the general population. Moreover, the use of extracorporeal therapeutic techniques like ECMO introduces further variability and unpredictability in drug behavior. This can result from factors such as drug depletion within ECMO circuits, altered drug distribution volumes, and reduced drug excretion.

Sepsis and septic shock due to infections like pneumonia are life-threatening conditions frequently requiring admission to intensive care units. Timely and effective antimicrobial therapy is vital to reduce morbidity and mortality. To investigate the impact of ECMO therapy on the PK and PD of antimicrobial drugs, this prospective observational study will collect blood samples from critically ill adult patients, both those receiving ECMO treatment and those not receiving it. The study will focus on various antimicrobial agents, including imipenem, vancomycin, piperacillin/tazobactam, ceftazidime/avibactam, cefoperazone/sulbactam, cefepime, ceftriaxone, ticlopidine, linezolid, tigecycline, amikacin, gentamicin, polymyxin, voriconazole, fluconazole, caspofungin, micafungin, levofloxacin, and moxifloxacin. Data collected will be used to develop a Population Pharmacokinetic and Pharmacodynamic model based on patient demographics, laboratory results, dosing information, and blood concentration data.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Jingjing Liu, Doctor; Phone Number: +86 0731-88618170; Email: ivljingjing@126.com
• Study Contact Backup: Name: Shengnan Zhang; Phone Number: +86 18084668240; Email: secnanzhang@gmail.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Third Hospital, Central South University
      • Contact: Jingjing Liu, Doctor; Phone Number: +86 0731-88618170; Email: ivljingjing@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Critically ill adult patients using one or more antimicrobial agents receiving or not receiving ECMO

Description

Inclusion Criteria:

1. Written informed consent was obtained from the patient or family member
2. Patients who are undergoing ECMO or not
3. Anti-infection treatment indications

Exclusion Criteria:

1. Patients under 18 years of age or pregnant
2. Information on antimicrobial therapy and ECMO support is incomplete
3. Presence of other circumstances that make participation in this study inappropriate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ECMO treatment group; Critically ill adult patients treated with ECMO using one or more antimicrobial agents	Device: ECMO treatment; Critically ill patients were treated with ECMO while receiving antimicrobial therapy
Non-ECMO treatment group; Critically ill adult patients using one or more antimicrobial agents not receving ECMO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood drug concentration	Plasma drug concentration	Samples were taken in the first 72 hours after administration according to the sampling schedule
Pharmacokinetic parameter	Area under the plasma concentration-time curve（AUC）	24 hours after administration
Pharmacokinetic parameter	Peak Plasma Concentration (Cmax)	12 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at 14 and 28 days	Mortality was measured by dividing the number of subjects who died during the observation period by the total number of subjects and multiplying by 100%.	Day 30 of the patient's admission

Collaborators and Investigators

• Sponsor: The Third Xiangya Hospital of Central South University
• Investigators: Study Chair: Jingjing Liu, Xiangya Third Hospital, Central South University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 17, 2023
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: ECMO; Critical Illness; Population Pharmacokinetics
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: Ivljingjing

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No