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

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04319328
• Other study ID #: H2019:031
• Status: Recruiting
• Start date: October 18, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2023
• Source: University of Manitoba
• Contact: Sheryl A Zelenitsky, PharmD
• Phone: 204-474-8414
• Email: zelenits[@]umanitoba.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• End Stage Renal Disease
• Hemodialysis Complication
• Infections
• Infectious Disease
• Kidney Failure, Chronic

Intervention

Drug:
• Cefazolin
Non-interventional pharmacokinetic evaluation
• Ceftazidime
Non-interventional pharmacokinetic evaluation
• Ciprofloxacin
Non-interventional pharmacokinetic evaluation

Locations

Country	Name	City	State
Canada	College of Pharmacy, University of Manitoba	Winnipeg	Manitoba
Canada	Saint Boniface Hospital, Outpatient Hemodialysis Unit	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
University of Manitoba	The Kidney Foundation of Canada

Country where clinical trial is conducted

Canada, 

Outcome

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