Drug Monitoring in Critically Ill Patients During Extracorporeal Life Support

February 8, 2020 updated by: Elisabeth H. Adam, Goethe University

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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasma concentration of antiinfective agents
Time Frame: 12 months
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Goethe University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 12, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 11, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings