Clinical trial NCT04083443: Model for PK/PD of Antimicrobials in Blood Stream Infection: Feasibility
Official title: Model Development for Pharmacokinetics / Pharmacodynamics of Antimicrobial Drugs in Blood Stream Infections Part 1: Feasibility Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Blood Stream Infections
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: University of Witten/Herdecke
name: University of Leipzig
name: University Hospital Munich
First posted: 2019-09-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For this study, patients with suspected blood stream infection will be enrolled.

Brief summary: The current study is a pilot study to assess the feasibility of a superordinate project. The final objective of this superordinate project is to describe and model the pharmacokinetic behaviour of a small number of standard antimicrobials used in the treatment of frequent blood stream infections, and to link this via pharmacodynamic models to (inhibition of) bacterial or fungal growth as well as to clinical outcomes in patients.

Detailed description: Patients with a high probability of a blood stream infection and an indication for antimicrobial treatment will be included. The study comprises the identification of patients as potential study participants, obtaining informed consent, documentation of available potential covariates from patient file, withdrawal of pre-study blood samples (PK, PD, microbiology) including documentation of exact time of sampling and processing of the samples, first drug administration including exact documentation (as part of patient care; not as a study intervention), withdrawal of subsequent blood samples (PK, PD, microbiology) during the next 3 days including documentation of exact time of sampling and processing of the samples, storage of processed samples for further analysis, and, if possible, documentation of patient outcome after 7 days. The following steps are carried out after completion of the clinical part of the study in the individual patient or, when possible, in all patients together or in a subset: Bioanalytics, DNA Counts, assessing primary and secondary study endpoints, pharmacometric analyses including PK parameter estimation, PD parameter estimation and assessment of covariate effects with regard to DNA count, CRP, IL-6 and procalcitonin.

Eligibility criteria: Inclusion Criteria:

* High probability of a blood stream infection; this is based on

  * the presence of SIRS \[Bone et al. 1992\] defined by more than one of the following clinical manifestations:

    1. a body temperature greater than 38°C or less than 36°C
    2. a heart rate greater than 90 beats per minute
    3. tachypnea, manifested by a respiratory rate greater than 20 breaths per minute, or hyperventilation, as indicated by a PaCO2 of less than 32 mm Hg
    4. an alteration in the white blood cell count, such as a count greater than 12,000/µl, a count less than 4,000/µl, or the presence of more than 10 percent immature neutrophils ("bands").

       and
  * the assessment of the treating physician according to the patient's situation that the SIRS is caused by an infection (e.g., patients after treatment with cytotoxic drugs)
* indication for antimicrobial treatment
* Intended use of one of the following antimicrobial agents:

piperacillin/tazobactam; vancomycin; meropenem; ampicillin/sulbactam; flucloxacillin; ceftriaxone; caspofungin (according to the decision of the project coordinator, use of other antimicrobial agents may also be included if anticipated to be used frequently)

* Age: 18 years or older (no upper limit)
* Willing and capable to provide written consent prior to enrolment after ample information has been provided

Exclusion Criteria:

* expected chances to successfully carry out venipunctures to obtain the blood samples required for the study are inadequately low according to the assessment of the physician
* Anemia CTCAE grade \>2 (i.e., Hb \<8.0 g/dL / 4.9 mmol/L)
* the clinical status of the patients suggests that the anticipated treatment of the patient or other conditions would make participation on the study inappropriate (e.g., terminally ill patients); the respective assessment is done by the treating physician

Primary outcomes:
measure: Fraction of eligible patients
timeFrame: Screening
measure: Positive blood microbial DNA count
timeFrame: Samples for DNA counts are taken for a duration of up to 3 days.
measure: Fraction of patients with at least three samples with microbial DNA
timeFrame: Samples for DNA counts are taken for a duration of up to 3 days.
measure: Plausible time courses of antimicrobial drug concentrations
timeFrame: Samples for antimicrobial drug concentrations are taken for a duration of up to 3 days.
Secondary outcomes:
measure: Population pharmacokinetic parameters of drugs studied
timeFrame: Samples for antimicrobial drug concentrations are taken for a duration of up to 3 days.
measure: Population pharmacodynamic parameters of drugs studied
timeFrame: Samples for antimicrobial drug concentrations are taken for a duration of up to 3 days.
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Klinik für Anaesthesiologie, Klinikum der Ludwig-Maximilians-Universität München
state: Bavaria
city: Cologne
country: Germany
facility: Clinical Infectiology, Klinik I für Innere Medizin, University Hospital Cologne
state: North Rhine-Westphalia
city: Cologne
country: Germany
facility: Klinik für Anästhesiologie und Operative Intensivmedizin Krankenhaus Köln-Merheim Klinikum der Universität Witten/ Herdecke
state: North Rhine-Westphalia
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR, Klinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie
state: Saxony
Study officials:
affiliation: Institut I für Pharmakologie, University of Cologne, Germany
name: Uwe D Fuhr, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: