Vancomycin Pharmacokinetics in Patients on Peritoneal Dialysis

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

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.

Study Overview

• Status: Completed
• Conditions: Peritoneal Dialysis-associated Peritonitis
• Intervention / Treatment: Drug: Vancomycin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin; A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period.	Drug: Vancomycin; Vancomycin one-time 20 mg/kg intraperitoneal dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Total Plasma Concentration (Cmax)	Total systemic plasma concentration following 12-hour dwell	Day: 1
Time to Maximum Plasma Concentration (Tmax)	Time (hours) to achieve the maximum plasma concentration	Day: 1
Area Under the Concentration-time Curve (AUC0-inf)	AUC based on vancomycin plasma concentrations	Days: 1-7
Total Body Clearance (CLtotal)	Total vancomycin plasma vancomycin clearance	Days: 1-7
Dialytic Clearance	Vancomycin clearance from peritoneal dialysis	Days: 1-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Any adverse events throughout entirety of study as assessed by physician-investigator	Days: 1-7

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

Publications and helpful links

General Publications

• 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. 2022 Mar;15(3):649-657. doi: 10.1111/cts.13182. Epub 2021 Nov 9.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Actual): August 30, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Vancomycin; Pharmacokinetics; Pharmacodynamics; Automated Peritoneal Dialysis
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: 12451

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual level PK de-identified data maybe shared
• IPD Sharing Time Frame: through 2024
• IPD Sharing Access Criteria: email. walter.kraft@jefferson.edu
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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