Clearance and Pharmacokinetics of Antibiotics in Renal Replacement Therapy

Completed

• Conditions: Kidney Failure
• Interventions: Other: Blood and spent dialysate collection

• Registration Number: NCT03714789
• Lead Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Brief Summary

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.

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 Timeline

• Study Start: 2017-11-01
• Study First Submitted: 2018-10-14
• Study First Submitted QC: 2018-10-18
• Study First Posted: 2018-10-22
• Primary Completion: 2019-12-30
• Status Verified: 2020-10
• Study Completion: 2020-10-01
• Last Update Submitted: 2020-10-23
• Last Update Posted: 2020-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Meropenem	Blood and spent dialysate collection	Patients requiring dialysis and receiving meropenem for infection or suspended infection.
Vancomycin	Blood and spent dialysate collection	Patients requiring dialysis and receiving vancomycin for infection or suspended infection.
Ceftriaxone	Blood and spent dialysate collection	Patients requiring dialysis and receiving ceftriaxone for infection or suspended infection.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Rebound of plasma concentration (Rebound_1h%)	At the end of dialysis and an hour after dialysis	The rebound rate of plasma concentration 1 hour after dialysis

Trial Locations

Locations (1)

Shanghai Ninth People's Hospital; 🇨🇳 Shanghai, China