Trial document





This trial has been registered retrospectively.
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  DRKS00008888

Trial Description

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Title

Therapeutic drug monitoring of Meropenem, Linezolide and Tigecyclin in liver failure. Quantification of liver function with Maximal Liver Function Capacity test (LiMAx-Test).

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Trial Acronym

LiMeS-study

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URL of the Trial

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Brief Summary in Lay Language

Critically ill patients frequently develop organ failure. Liver dysfunction is measured with laboratory parameters, which cannot approve a reliable information about the degree of liver dysfunction. Antibiotic therapy of critically ill patients appears as a specific challenge for intensive care specialists. In septic patients antibiotic therapy is, beside elimination of the septic focus, the most important intervention on intensive care unit.
For the most antibiotic drugs, serum drug levels are not available in routine. In liver failure, the exact dosage of hepatic metabolised drugs is not known due to absent data. Thus, under dosage with the risk of therapeutic failure or over dosage with the risk of toxic side effects are possible.
The Maximal Liver Function Capacity test (LiMAx test) provides the measurement of quantitative liver function. Data of several studies showed a favorable correlation between liver function and quantitative test results.
The aim of the study is the investigation of the correlation between quantitative liver function, measured by LiMAx test, and the serum levels of the antibiotics.
Hypothesis: The degree of liver function meaasured by LiMAx test correlates with the serum drug levels.
Primary endpoint: Correlation between LiMAx test and serum drug level.

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Brief Summary in Scientific Language

Critically ill ICU-patients are at high risk of developing nosocomial infections (sepsis). Beside early and appropriate use of antimicrobial drugs, adequate dosage of antibiotics are crucial for bacterial elimination. Patients on ICU often develop organ dysfunctions. In concert with drug interactions and other therapeutic interventions, organ dysfunction can lead to changes in pharmacokinetics of antibiotic substances. While renal failure can be measured accurately with endogen creatinine clearance, no valid tests exists until recently to determine the liver failure. The now introduced Maximal Liver Function Capacity test (LiMAx-test) provides a reliable tool for quantification of liver function.
The aim of this study is to analyze the correlation between antibiotic drug levels and liver dysfunction for the first time. Therefor three antibiotic substances (Meropenem, Linezolid, Tigecycline) used in ICU setting and which are partly eliminated by the liver, will be investigated. In each antibiotic arm 105 patients with indication for therapy with the certain antibiotic and with assumed liver failure, and 35 patients with normal liver function will be prospectively examined. Hepatic function will be quantified with the novel LiMAx test. Renal function will be measured with the endogen creatinine clearance. Renal drug elimination will be assessed by measurement of drug levels in spot-urine and day-collected urine. If continuous renal replacement therapy is indicated, drug elimination by dialysis will be calculated with the measurement of dialysate-level. Hence, antibiotic drug level can be determined not only as an absolute value, but also the correlation between renal clearance, non-renal clearance, dialysis clearance and total drug clearance can be investigated.
Sample collection will be performed on an exact defined time point. LiMAx test will be carried out on the same day. After preparation samples will be frozen by -80°C. Measurement of drug levels will be performed as batch measurements every three months using High-Performance-Liquid-Chromatographie (HPLC). According to the results of the LiMAx test, liver dysfunction will be divided into three severity levels and one group of normal function. Results of the different groups will be statistically investigated. The following hypothesis are developed: (i) Patients with liver dysfunction show higher drug level than patients with normal liver function. (ii) There is a correlation between severity of liver dysfunction and height of drug level.
The present study may prove for the first time, that hepatic eliminated antibiotic drugs accumulate in patients with liver dysfunction. These drugs should be adapted to the liver function.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00008888
  •   2015/07/17
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  •   yes
  •   Approved
  •   EA4/022/13, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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Health Condition or Problem studied

  •   K72.0 -  Acute and subacute hepatic failure
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Interventions/Observational Groups

  •   Measurement of liver function with LiMAx test (Maximal Liver Function Capacity Test) and therapeutic drug Monitoring (Serum, Urine, Dialysat) in critically ill patients with assumed liver dysfunction and indication of antibiotic therapy (Meropenem, Linezolide, Tigecycline)
  •   Measurement of liver function with LiMAx test (Maximal Liver Function Capacity Test) and therapeutic drug Monitoring (Serum, Urine, Dialysat) in critically ill patients with indication of antibiotic therapy (Meropenem, Linezolide, Tigecycline) and without liver dysfunction.
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Characteristics

  •   Non-interventional
  •   Other
  •   Other
  •   Open (masking not used)
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  •   Other
  •   Other
  •   Other
  •   N/A
  •   No
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Primary Outcome

Correlation between quantitative liver function measured by LiMAx-test and Serum-Drug-Level (Meropenem, Linezolide or Tigecycline) after maintaining a constant drug Level (>36h after beginning of antibiotic therapy)

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Secondary Outcome

Improvement of dosage of hepatic metabilised antibiotics in liver failure

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2014/03/22
  •   420
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   90   Years
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Additional Inclusion Criteria

1. Existence of liver failure and indication of therapy with Meropenem, Linezolide or Tigecycline
2. Age >18<90
3. Existing inform consent (patient or legal caregiver)

Control Group:
1.Indication of therapy with Meropenem, Linezolide or Tigecycline and absence of liver failure
2. Age >18<90
3. Existing inform consent (patient or legal caregiver)

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Exclusion Criteria

1. Allergy against Methacetin
2. Age <18>90
3. Pregnancy, breast feeding
3. Missing inform consent
4. patient cannot cooperate during study due to mental disturbance

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Addresses

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    • Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum. Klinik für Allgemein-, Visceral, und Transplantationschirurgie
    • Mr.  Dr. med.  Magnus  Kaffarnik 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum. Klinik für Allgemein-, Visceral, und Transplantationschirurgie
    • Mr.  Dr. med.  Magnus  Kaffarnik 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
    • Mr.  Dr. med.  Magnus  Kaffarnik 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Charité Campus Virchow-Klinikum
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.