Is Cefazolin, Ceftazidime and Ciprofloxacin Dosing Optimal in Hemodialysis Patients?

May 14, 2024 updated by: Sheryl Zelenitsky, University of Manitoba

Pharmacokinetic Evaluation of Cefazolin, Ceftazidime, and Ciprofloxacin in Chronic Hemodialysis Patients

This study aims to optimize the dosing of cefazolin, ceftazidime, and ciprofloxacin for patients on high-flux hemodialysis. For each antibiotic 20 participants will be enrolled and three blood samples will be collected from each participant. Antibiotic levels will be measured in each blood sample. This data will be used to develop population-pharmacokinetic models for each antibiotic. Finally, Monte Carlo simulations will be used to develop evidence-based dosing recommendations.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The goal of this study is to optimize the dosing of three commonly used antibiotics, thereby improving the treatment of serious, often life-threatening infections in patients on intermittent high-flux hemodialysis (iHFHD).

The hypothesis is that current antibiotic dosing is suboptimal, thereby increasing the risk of poor outcomes including treatment failure, adverse drug reactions and antibiotic resistance.

A prospective, non-interventional pharmacokinetic (PK) study of cefazolin, ceftazidime, and ciprofloxacin will be conducted in the St. Boniface Hospital outpatient hemodialysis unit.

The 1st objective of this study is to measure the free and total plasma concentrations of cefazolin, ceftazidime, and ciprofloxacin in adult patients on iHFHD and receiving antibiotic therapy for suspected or proven infection. For each antibiotic 20 participants will be enrolled and three blood samples will be collected from each participant. Antibiotic concentrations will be measured using an ultra high performance liquid chromatograph mass spectrometer. Total antibiotic concentrations in plasma will be measured in all patient samples. To describe protein binding, free levels will also be measured in the first two samples collected from the first 10 patients for each antibiotic.

The 2nd objective of this study is to characterize the PK of cefazolin, ceftazidime, and ciprofloxacin in patients on iHFHD using population-PK modelling. Covariates with potential influence on PK such as gender, age, body weight, dialyzer type, blood and dialysate flow rates, duration of dialysis and Kt/Vurea will be investigated, and incorporated as appropriate. For each antibiotic, the best PK model will be selected using established goodness-of-fit tests, and then independently validated.

The 3rd objective of this study is to translate findings to patient care using Monte Carlo simulations to evaluate conventional antibiotic dosing and develop optimized evidence-based dosing recommendations for cefazolin, ceftazidime, and ciprofloxacin in patients on iHFHD.

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
        • Saint Boniface Hospital, Outpatient Hemodialysis Unit
      • Winnipeg, Manitoba, Canada, R3E 0T5
        • College of Pharmacy, University of Manitoba

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients on chronic intermittent high-flux hemodialysis being treated for infection.

Description

Inclusion Criteria:

  • >18 years old
  • Proven or suspected infection
  • Receiving cefazolin, ceftazidime, or ciprofloxacin for treatment
  • Treatment course allows for collection of three 6 mL blood samples as per protocol

Exclusion Criteria:

  • Chronic liver disease, Child Pugh Class C or higher
  • Received study drug as part of a different treatment course in 1-week preceding start of new treatment course
  • Acute kidney injury or recovering kidney function

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cefazolin
n = 20
Drug: Cefazolin
Non-interventional pharmacokinetic evaluation
Ceftazidime
n = 20
Drug: Ceftazidime
Non-interventional pharmacokinetic evaluation
Ciprofloxacin
n = 20
Drug: Ciprofloxacin
Non-interventional pharmacokinetic evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volume of distribution (Vd) for cefazolin, ceftazidime, and ciprofloxacin in infected patients on chronic intermittent high-flux hemodialysis.
Time Frame: 48 to 72 hours
48 to 72 hours
Drug elimination (ke) for cefazolin, ceftazidime, and ciprofloxacin in infected patients on chronic intermittent high-flux hemodialysis.
Time Frame: 48 to 72 hours
Drug elimination (ke) during and between dialysis sessions
48 to 72 hours
Drug clearance (CL) for cefazolin, ceftazidime, and ciprofloxacin in infected patients on chronic intermittent high-flux hemodialysis.
Time Frame: 48 to 72 hours
48 to 72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Collaborators

The Kidney Foundation of Canada

Investigators

  • Principal Investigator: Sheryl A Zelenitsky, PharmD, University of Manitoba

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2019

Primary Completion (Actual)

April 30, 2024

Study Completion (Actual)

April 30, 2024

Study Registration Dates

First Submitted

March 2, 2020

First Submitted That Met QC Criteria

March 23, 2020

First Posted (Actual)

March 24, 2020

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 14, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H2019:031

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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