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

Blood Stream Infections Clinical Trial

— MOBSI1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04083443
• Other study ID #: MOBSI1
• Status: Recruiting
• Start date: July 23, 2019
• Est. completion date: August 2021

Study information

• Verified date: September 2019
• Source: University of Cologne
• Contact: Uwe Fuhr, Prof. Dr.
• Phone: +49 221 478 5230
• Email: uwe.fuhr[@]uk-koeln.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Blood Stream Infections
• Communicable Diseases
• Infection

Intervention

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.

Locations

Country	Name	City	State
Germany	Clinical Infectiology, Klinik I für Innere Medizin, University Hospital Cologne	Cologne	North Rhine-Westphalia
Germany	Klinik für Anästhesiologie und Operative Intensivmedizin Krankenhaus Köln-Merheim Klinikum der Universität Witten/ Herdecke	Cologne	North Rhine-Westphalia
Germany	Universitätsklinikum Leipzig AöR, Klinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie	Leipzig	Saxony
Germany	Klinik für Anaesthesiologie, Klinikum der Ludwig-Maximilians-Universität München	Munich	Bavaria

Sponsors (4)

Lead Sponsor	Collaborator
University of Cologne	University Hospital Munich, University of Leipzig, University of Witten/Herdecke

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fraction of eligible patients	Fraction of identified and potentially eligible patients willing and able to provide informed consent	Screening
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.