Clearance and Pharmacokinetics of Antibiotics in Renal Replacement Therapy

Kidney Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03714789
• Other study ID #: PKDialysis-201710
• Status: Completed
• Start date: November 1, 2017
• Est. completion date: October 1, 2020

Study information

• Verified date: October 2020
• Source: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 1, 2020
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Failure
• Renal Insufficiency

Intervention

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.

Locations

Country	Name	City	State
China	Shanghai Ninth People's Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University	Institute of Antibiotics, Huashan Hospital, Fudan University

Country where clinical trial is conducted

China, 

Outcome

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