Vancomycin Pharmacokinetics in Patients on Peritoneal Dialysis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Peritoneal Dialysis-associated Peritonitis

Intervention / Treatment
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* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vancomycin<br>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<br>* Vancomycin one-time 20 mg/kg intraperitoneal dose.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vancomycin, Pharmacokinetics, Pharmacodynamics, Automated Peritoneal Dialysis