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

NCT ID: NCT04319328

Last Updated: 2024-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-10-18

Study Completion Date

2024-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hemodialysis Complication Infectious Disease End Stage Renal Disease

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Cefazolin

n = 20

Cefazolin

Intervention Type DRUG

Non-interventional pharmacokinetic evaluation

Ceftazidime

n = 20

Ceftazidime

Intervention Type DRUG

Non-interventional pharmacokinetic evaluation

Ciprofloxacin

n = 20

No interventions assigned to this group

Interventions

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Cefazolin

Non-interventional pharmacokinetic evaluation

Intervention Type DRUG

Ceftazidime

Non-interventional pharmacokinetic evaluation

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Kidney Foundation of Canada

OTHER

Sponsor Role collaborator

University of Manitoba

OTHER

Sponsor Role lead

Responsible Party

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Sheryl Zelenitsky

Professor, College of Pharmacy, Rady Faculty of Health Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sheryl A Zelenitsky, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

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Saint Boniface Hospital, Outpatient Hemodialysis Unit

Winnipeg, Manitoba, Canada

Site Status

College of Pharmacy, University of Manitoba

Winnipeg, Manitoba, Canada

Site Status

Countries

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Canada

Other Identifiers

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H2019:031

Identifier Type: -

Identifier Source: org_study_id

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