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

NCT ID: NCT04083443

Last Updated: 2020-01-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-07-23
• Study Completion Date: 2021-08-31

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.

Conditions

Blood Stream Infections

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Additional blood sampling

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Witten/Herdecke

OTHER

Sponsor Role: collaborator

University of Leipzig

OTHER

Sponsor Role: collaborator

University Hospital Munich

OTHER

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Uwe Fuhr

Director, Department I of Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Uwe D Fuhr, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Institut I für Pharmakologie, University of Cologne, Germany

Locations

Klinik für Anaesthesiologie, Klinikum der Ludwig-Maximilians-Universität München

Munich, Bavaria, Germany

Site Status: NOT_YET_RECRUITING

Clinical Infectiology, Klinik I für Innere Medizin, University Hospital Cologne

Cologne, North Rhine-Westphalia, Germany

Site Status: RECRUITING

Klinik für Anästhesiologie und Operative Intensivmedizin Krankenhaus Köln-Merheim Klinikum der Universität Witten/ Herdecke

Cologne, North Rhine-Westphalia, Germany

Site Status: NOT_YET_RECRUITING

Universitätsklinikum Leipzig AöR, Klinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie

Leipzig, Saxony, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Uwe Fuhr, Prof. Dr.

Role: CONTACT

uwe.fuhr@uk-koeln.de

+49 221 478 5230

Dario Zaremba, Dr.

Role: CONTACT

dario.zaremba@uk-koeln.de

+49 221 478 6064

Facility Contacts

Michael Zoller, Dr.

Role: primary

michael.zoller@med.uni-muenchen.de

+49 89 4400 74551

Norma Jung, PD Dr.

Role: primary

norma.jung@uk-koeln.de

+49 221 478 3324

Samir Sakka, Prof. Dr.

Role: primary

sakkas@kliniken-koeln.de

+49 221 8907 13430

Niklas Aehling, Dr.

Role: primary

niklas.aehling@medizin.uni-leipzig.de

+49 341 97 12333

Adam Herber

Role: backup

adam.herber@medizin.uni-leipzig.de

Other Identifiers

MOBSI1

Identifier Type: -

Identifier Source: org_study_id