Vancomycin Pharmacokinetics in Patients on Peritoneal Dialysis

Peritoneal Dialysis-associated Peritonitis Clinical Trial

Official title:

A Prospective, Single-site, Open-label, Pharmacokinetic Study of Intermittent Intraperitoneal Vancomycin in Adult Subjects Receiving Automated Peritoneal Dialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03685747
• Other study ID #: 12451
• Status: Completed
• Phase: Phase 1
• Start date: November 15, 2018
• Est. completion date: October 1, 2020

Study information

• Verified date: March 2022
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Vancomycin is the most commonly used empiric treatment for infectious peritonitis in patients on peritoneal dialysis. Current dosing and monitoring for safety and efficacy is empiric, especially for those on rapid-cycling modalities. The goal of this study is to understand the pharmacokinetics of vancomycin in patients on rapid-cycling peritoneal dialysis modalities in order to derive an optimal dosing regimen.

Description:

Peritoneal dialysis (PD) is a form of renal replacement therapy indicated for those with acute kidney injury or end stage renal disease. Currently, two modalities of PD exist and is individualized based on patient and life-style specific factors. Continuous ambulatory peritoneal dialysis (CAPD) allows 4 - 5 exchanges performed manually whereas automated peritoneal dialysis (APD) involves continuous, automated, cyclical exchanges performed by a device at home during the night. Peritonitis is a common complication in PD and accounts for a large portion of hospital readmission and mortality. Vancomycin is the most common antibiotic recommended and has notable gram-positive coverage used empirically during suspected peritonitis.

Despite widespread use, vancomycin lacks good pharmacokinetic characterization in PD. Early pharmacokinetic studies using vancomycin were conducted predominantly in patients on CAPD on glucose-based prescriptions. Data is non-existent in PD patients administered the novel dialysate solution icodextrin, or those treated with overnight APD. The impact of residual kidney function (RKF) on vancomycin in PD is also lacking. Enhanced vancomycin clearance in RKF may result in under-dosing, while overdosing may result in nephrotoxicity and loss of clinically important RKF.

The investigators will characterize the pharmacokinetic profile of vancomycin following a single intraperitoneal dose of vancomycin in icodextrin dialysate to non-infected PD patients and examine the relationship between RKF and vancomycin clearance using serum, dialysate and urine. The goal is to use this data in non-infected subjects to generate information to guide vancomycin dosing in patients on rapid-cycling PD modalities.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: October 1, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Adult male or females between 18 - 85 years old

• Stabilized on a PD regimen for > 3 months prior to study initiation

Exclusion Criteria:

• Clinically significant disease unrelated to renal impairment or deemed unfit by the investigator

• Allergy or hypersensitivity to vancomycin or icodextrin-containing dialysis solution

• Active peritonitis infection

• Previous intraperitoneal antibiotic treatment within 2 months

• Previous intravenous vancomycin treatment within 2 months

• Hemoglobin < 9 g/dL

• Pregnant or breast-feeding women

Related Conditions & MeSH terms

• Peritoneal Dialysis-associated Peritonitis
• Peritonitis

Intervention

Drug:
• Vancomycin
Vancomycin one-time 20 mg/kg intraperitoneal dose.

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lam E, Ting Kayla Lien Y, Kraft WK, Stickle DF, Piraino B, Zhang J. Intraperitoneal pharmacokinetics of vancomycin in patients on automated peritoneal dialysis. Clin Transl Sci. 2021 Nov 9. doi: 10.1111/cts.13182. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Total Plasma Concentration (Cmax)	Total systemic plasma concentration following 12-hour dwell	Day: 1
Primary	Time to Maximum Plasma Concentration (Tmax)	Time (hours) to achieve the maximum plasma concentration	Day: 1
Primary	Area Under the Concentration-time Curve (AUC0-inf)	AUC based on vancomycin plasma concentrations	Days: 1-7
Primary	Total Body Clearance (CLtotal)	Total vancomycin plasma vancomycin clearance	Days: 1-7
Primary	Dialytic Clearance	Vancomycin clearance from peritoneal dialysis	Days: 1-7
Secondary	Adverse Events	Any adverse events throughout entirety of study as assessed by physician-investigator	Days: 1-7