Model for PK/PD of Antimicrobials in Blood Stream Infection: Feasibility (MOBSI1)

Model Development for Pharmacokinetics / Pharmacodynamics of Antimicrobial Drugs in Blood Stream Infections Part 1: Feasibility Study

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.

Study Overview

• Status: Unknown
• Conditions: Blood Stream Infections
• Intervention / Treatment: Other: Additional blood sampling

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.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • Not yet recruiting
      • Klinik für Anaesthesiologie, Klinikum der Ludwig-Maximilians-Universität München
      • Contact: Michael Zoller, Dr.; Phone Number: +49 89 4400 74551; Email: michael.zoller@med.uni-muenchen.de
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Recruiting
      • Clinical Infectiology, Klinik I für Innere Medizin, University Hospital Cologne
      • Contact: Norma Jung, PD Dr.; Phone Number: +49 221 478 3324; Email: norma.jung@uk-koeln.de
    • Cologne, North Rhine-Westphalia, Germany, 51109
      • Not yet recruiting
      • Klinik für Anästhesiologie und Operative Intensivmedizin Krankenhaus Köln-Merheim Klinikum der Universität Witten/ Herdecke
      • Contact: Samir Sakka, Prof. Dr.; Phone Number: +49 221 8907 13430; Email: sakkas@kliniken-koeln.de
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Recruiting
      • Universitätsklinikum Leipzig AöR, Klinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie
      • Contact: Niklas Aehling, Dr.; Phone Number: +49 341 97 12333; Email: niklas.aehling@medizin.uni-leipzig.de
      • Contact: Adam Herber; Email: adam.herber@medizin.uni-leipzig.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

For this study, patients with suspected blood stream infection will be enrolled.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with blood stream infections; Patients with a high probability of a blood stream infection and an indication for antimicrobial treatment. There will be an additional blood sampling for these patients, which is the only intervention in the study.	Other: Additional blood sampling; Blood samples will be taken to assess antimicrobial drug concentrations and microbial DNA blood counts. Per patient, at least 5 and up to 15 samples for drug concentrations and at least 3 and up to 6 samples for DNA counts are taken for a duration of up to 3 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fraction of eligible patients	Fraction of identified and potentially eligible patients willing and able to provide informed consent	Screening
Positive blood microbial DNA count	Fraction of study participants having any positive blood microbial DNA count for microbes which does not reflect sample contamination	Samples for DNA counts are taken for a duration of up to 3 days.
Fraction of patients with at least three samples with microbial DNA	Fraction of study participants with at least three samples with quantifiable microbial DNA along with a proper documentation	Samples for DNA counts are taken for a duration of up to 3 days.
Plausible time courses of antimicrobial drug concentrations	Fraction of study participants with plausible time courses of antimicrobial drug concentrations along with a proper documentation	Samples for antimicrobial drug concentrations are taken for a duration of up to 3 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population pharmacokinetic parameters of drugs studied	Pharmacometric analyses including PK parameter estimation	Samples for antimicrobial drug concentrations are taken for a duration of up to 3 days.
Population pharmacodynamic parameters of drugs studied	Population pharmacodynamic parameters of drugs studied with regard to bacterial DNA count, procalcitonin, IL-6 and C-reactive protein	Samples for antimicrobial drug concentrations are taken for a duration of up to 3 days.

Collaborators and Investigators

• Sponsor: University of Cologne
• Collaborators: University of Leipzig; University of Witten/Herdecke; University Hospital Munich
• Investigators: Principal Investigator: Uwe D Fuhr, Prof. Dr., Institut I für Pharmakologie, University of Cologne, Germany

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 16, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Infections; Communicable Diseases
• Other Study ID Numbers: MOBSI1

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