Trial document




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  DRKS00007479

Trial Description

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Title

Prospective study on plasma levels of linezolid in septic patients dependent on liver funtion measured by plasma disappearance rate of indocyanine green

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Trial Acronym

LINESEP-Liver

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Linezolid is an antibiotic of last resort used in ICU to treat severe infections. The major route of elimination is exceretion by the liver into bile. Patients with severe infection often develop multi organ dysfunctions, e.g. liver dysfunction. Dose recommendations for antibiotics are often derived from study on healthy individuals without organ dysfunction.
In this study linezolid levels are measured in ICU patients and a dependence of the levels on liver function is studied, in oder to be elaborate dose recommendations for this patient cohort.

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Brief Summary in Scientific Language

Serum levels of antibiotics in critically ill patients are not predictable due to complex pathophysiologic alterations. Changes in volume of distribution and clearance in renal and hepatic dysfunction are common in septic patients and lead to unique tissue concentrations of antibiotics and thereby to potential inappropriate dosage. Liver dysfunction may result in higher plasma levels and higher hepatocellular concetrations in antibiotics eliminated via the liver leading to further hepatocellular dysfunction.
We will assess linezolid serum levels in steady state of septic patients and will correlate them with liver function. Liver function will be assessed by measuring plasma disappearance rate of indocyanine green.
Sample size analysis revealed n=18 necessary patients. To compensate for drop outs 22 patients were planned.

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Organizational Data

  •   DRKS00007479
  •   2014/12/12
  •   [---]*
  •   yes
  •   Approved
  •   3424-04/12, Ethikkommission der Friedrich-Schiller-Universität Jena an der Medizinischen Fakultät
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Secondary IDs

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Health Condition or Problem studied

  •   A41.9 -  Sepsis, unspecified
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Interventions/Observational Groups

  •   In patients with linezolid therapy blood samples will be drawn in steady state once before application of linezolid (T0) as well as approximately 0.5 h (T1), 1.5 h (T2), 3h (T3), 6h (T4) and 12h (T5) after application.
    In addition up to 6h before T0 plasma disappearance rate of indocyanine green will be assessed.
    In patients with bile drainage bile concentration of linezolid will be assessed at the time points T0 -T5.
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Characteristics

  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   N/A
  •   No
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Primary Outcome

course of linezolid serum levels (before appl., approx. 0.5 h, 1.5 h, 3h, 6h and 12h after appl.) in steady state (after 4th, 5th, 6th or 7th application) dependent on liver function, assessed by plasma disappearance rate of indocyanine green up to 6h before application.

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Secondary Outcome

-course of linezolid serum levels in steady state in severe sepsis and/or septic shock,
-AUC0-24/MIC
-clinical cure
course of organ failure (SoFA score and subscores)
-laboratory parameters of infection on day 7 (PCT, CRP, WBC)
-Hospital and ICU mortality and stay
-subgroup: bile concentration of linezolid

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2014/12/12
  •   22
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- antibiotic treatment with linezolid indicated by physician in charge
- severe sepsis and/or septic shock
- intensive care therapy

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Exclusion Criteria

-renal failure with renal replacement therapy
-pregnancy, lactation period
-participation in an interventional study
-restriction of therapeutic measures (e.g. DNR (do-not-resuscitate) order)
-staff and their relatives
-Hyperthyreosis
-allergy against iodine

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Addresses

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    • Universitätsklinikum Jena
    • Bachstraße 18
    • 07740  Jena
    • Germany
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    • Universitätsklinikum Jena - Klinik für Anästhesiologie und Intensivtherapie
    • Mr.  PD Dr.  Andreas  Kortgen 
    • Erlanger Allee 101
    • 07747  Jena
    • Germany
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    • Universitätsklinikum Jena - Klinik für Anästhesiologie und Intensivtherapie
    • Mr.  PD Dr.  Andreas  Kortgen 
    • Erlanger Allee 101
    • 07747  Jena
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung (BMBF) Dienstsitz Berlin
    • Friedrichstraße 130 B
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting planned
  •   [---]*
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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.