Drug Monitoring in Critically Ill Patients During Extracorporeal Life Support

Drug Monitoring of Antiinfectives in Critically Ill Patients Receiving Extracorporeal Life Support - a Prospective Observational Pilot Study

About 70% of critically ill patients require antiinfective therapy. Optimal antibiotic dosing is key to improve patient survival, reduce toxic effects and minimise the emergence of bacterial resistance. There is a growing body of evidence demonstrating the existence of significant changes in pharmacokinetics (PK) in intensive care patients, particularly those with extracorporeal therapy (extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT)). To characterize the effects of extracorporal therapy for critically ill patients, we designed a prospective pilot observational study using a drug monitoring to derive relevant effects of extracorporeal therapy and clinical patient characteristics for the treatment with meropenem, teicoplanin, linezolid, piperacillin/tazobactam, levofloxacin and acyclovir.

Study Overview

• Status: Unknown
• Conditions: Drug Monitoring of Antiinfectives in Critically Ill Patients Receiving Extracorporeal Life Support
• Intervention / Treatment: Other: No Intervention

Detailed Description

About 70% of critically ill patients require antiinfective therapy. Optimal antibiotic dosing is key to improve patient survival, reduce toxic effects and minimise the emergence of bacterial resistance. However, there is a growing body of evidence demonstrating the existence of significant changes in pharmacokinetics (PK) in intensive care patients, particularly those with extracorporeal therapy (extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT)). Existing antiinfectivedosing regimens assume a "normal" PK; currently there are no evidence-based antiinfective dosing guidelines for critically ill patients available. The current recommendations of the Paul-Ehrlich Society and the Surviving Sepsis Campaign therefore recommend explicitly appliance of a therapeutic drug monitoring (TDM) for intensive care patients to individually adjust dosing and to avoid potential over- or underdosing. To characterize the effects of extracorporal therapy for critically ill patients, we designed a prospective pilot observational study using a drug monitoring. Six antiinfectives (meropenem, teicoplanin, linezolid, piperacillin / tazobactam, levofloxacin and aciclovir) will be investigated as index substances for the various antiinfective groups. A total of 100 patients, divided into 5 groups of 20 patients, will be examined in this study: 1. venovenous (vv)-ECMO, 2. venoarterial (va)-ECMO, 3. vv-ECMO + CRRT, 4. va-ECMO + CRRT, 5. control group. Sampling for determination of trough and peak levels of the study substances will take place during the different dosing intervals. Patients will be included at the beginning of ECMO therapy within 24-48h after start of an antiinfective therapy with at least one of the index-substances; observation period will be a total of 5 days. The collected data will be analyzed to identify covariates associated with changes in PK for the 6 different antiinfectives in critically ill patients receiving extracorporeal therapy. Using the comprehensive data set collected, the pharmacokinetic profile of the 6 antiinfectives as well as other influencing factors will be constructed to assess the need for dose adjustment of antiinfective agents in these patients. This prospective observational trial addresses the current knowledge deficiency with the aim to derive relevant effects of extracorporeal therapy and clinical patient characteristics for the treatment with meropenem, teicoplanin, linezolid, piperacillin/tazobactam, levofloxacin and acyclovir. With these relevant results, adapted dosing of antiinfectives can probably be improved in critically ill patients with extracorporeal therapy in future.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Germany
  • Deutschland
    • Frankfurt am Main, Deutschland, Germany, 60529
      • Recruiting
      • Universital Hospital Frankfurt / Main
      • Contact: Elisabeth H. Adam, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

critically ill patients with extracorporeal heart or lung support and possibly CRRT

Description

Inclusion Criteria:

• Age > 18
• Informed consent
• Clinical infection indicated for intravenous therapy with at least one of the following index anti-infectives: meropenem, teicoplanin, linezolid, piperacillin/tazobactam, levofloxacin and/oraciclovir
• Application of an ECLS procedure with an expected duration of at least five days

Exclusion Criteria:

• Pregnancy
• Massive Hemorrhage

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
VA ECMO; Patients will be included at the beginning of VA ECMO therapy within 24-48h after start of an antiinfective therapy	Other: No Intervention; No Intervention
VA EMCO + RRT; Patients with RRT will be included at the beginning of VA ECMO therapy within 24-48h after start of an antiinfective therapy	Other: No Intervention; No Intervention
VV ECMO; Patients will be included at the beginning of VV ECMO therapy within 24-48h after start of an antiinfective therapy	Other: No Intervention; No Intervention
VV ECMO + RRT; Patients with RRT will be included at the beginning of VV ECMO therapy within 24-48h after start of an antiinfective therapy	Other: No Intervention; No Intervention
Control; Patients will be included within 24-48h after start of an antiinfective therapy	Other: No Intervention; No Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of antiinfective agents	pharmacokinetic profile of 6 antiinfectives (meropenem, teicoplanin, linezolid, piperacillin / tazobactam, levofloxacin and aciclovir) as well as other influencing factors will be constructed to assess the need for dose adjustment of antiinfective agents	12 months

Collaborators and Investigators

• Sponsor: Goethe University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): May 31, 2022

Study Registration Dates

• First Submitted: October 12, 2019
• First Submitted That Met QC Criteria: October 12, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 8, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: ECMO; intensive care; drug monitoring; antiinfectives
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: Drug Monitoring during ECMO

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