Clearance and Pharmacokinetics of Antibiotics in Renal Replacement Therapy

Clearance and Pharmacokinetics of Antibiotics With Different Protein-bound Levels in Renal Replacement Therapy

This is an observational study that evaluates the dialysis clearance and pharmacokinetics of antibiotics with different protein-bound levels in patients receiving renal replacement therapy. Meropenem, vancomycin and ceftriaxone are selected to represent three typical protein-bound levels, and the primary dialysis methods being studied are intermittent hemodialysis(IHD) and hemodiafiltration(HDF). During and after the dialysis, the drug levels in both plasma and spent dialysate are monitored, but no changes are made to therapy. The study will provide detailed information on the characteristics of the removal kinetics of the three antibiotics during dialysis, and evaluate whether the dosing regimens are the most appropriate to achieve therapeutic targets while minimizing the risk of toxicity.

Study Overview

• Status: Completed
• Conditions: Kidney Failure
• Intervention / Treatment: Other: Blood and spent dialysate collection

Detailed Description

This prospective, single-center observational study is taken to evaluate the dialysis clearance and pharmacokinetics of antibiotics with three different protein-bound levels in patients receiving renal replacement therapy. As is known that the plasma protein binding rate affects the distribution, metabolism and elimination of the drug in the body, and is also an important factor affecting the removal during dialysis, the study selects meropenem, vancomycin and ceftriaxone, of which the protein-bound levels are respectively 2%, 55% and 85%, to represent three typical protein-bound levels. The primary dialysis methods being studied are intermittent hemodialysis(IHD) and hemodiafiltration(HDF). The dialysis pattern, the antibiotic choice and its dosage for each subject are made on clinical grounds. A total of 16 milliliters of blood and 60 milliliters of spent dialysate are collected from each subject for each dialysis pattern. The study will provide detailed information on the characteristics of the removal kinetics of the three antibiotics during dialysis, and evaluate whether the dosing regimens are the most appropriate to achieve therapeutic targets while minimizing the risk of toxicity.

• Study Type: Observational
• Enrollment (Actual): 19

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Ninth People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients aged from 18 to 85 years, requiring dialysis including intermittent hemodialysis(IHD) or hemodiafiltration(HDF), and receiving meropenem, vancomycin or ceftriaxone based on clinical grounds from a university-affiliated hospital in Shanghai, China.

Description

Inclusion Criteria:

• With Age from 18 to 85 years old.
• With weight from 50 to 75 kilograms.
• Requiring dialysis including intermittent hemodialysis(IHD) or hemodiafiltration(HDF).
• Receiving meropenem, vancomycin or ceftriaxone based on clinical grounds.

Exclusion Criteria:

• Patient is during pregnant or lactation period.
• Patient is allergic to meropenem, vancomycin or ceftriaxone.
• Severe hypoproteinemia (serum total protein<=45g/L) or severe hypoalbuminemia（serum albumin<20g/L).
• Severe liver dysfunction（ALT>200U/L or AST>200U/L).
• The patient himself or his immediate family refuses to sign the informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Meropenem; Patients requiring dialysis and receiving meropenem for infection or suspended infection.	Other: Blood and spent dialysate collection; A certain amount of blood and spent dialysate are collected during and after dialysis for quantification of drug concentration.
Vancomycin; Patients requiring dialysis and receiving vancomycin for infection or suspended infection.	Other: Blood and spent dialysate collection; A certain amount of blood and spent dialysate are collected during and after dialysis for quantification of drug concentration.
Ceftriaxone; Patients requiring dialysis and receiving ceftriaxone for infection or suspended infection.	Other: Blood and spent dialysate collection; A certain amount of blood and spent dialysate are collected during and after dialysis for quantification of drug concentration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dialytic clearance (K_total)	The total drug amount removed by dialysis	During the session of dialysis, up to 4 hours
Area under the concentration-time curve (AUC)	AUC based on plasma concentration during dialysis	During the session of dialysis, up to 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rebound of plasma concentration (Rebound_1h%)	The rebound rate of plasma concentration 1 hour after dialysis	At the end of dialysis and an hour after dialysis

Collaborators and Investigators

• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Collaborators: Institute of Antibiotics, Huashan Hospital, Fudan University
• Investigators: Study Director: Feng Ding, PhD, Division of Nephrology,Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: October 14, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Antibiotics; Kidney Failure
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Pharmaceutical Solutions; Dialysis Solutions
• Other Study ID Numbers: PKDialysis-201710

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No