Clinical trial NCT03685747: Vancomycin Pharmacokinetics in Patients on Peritoneal Dialysis
Official title: A Prospective, Single-site, Open-label, Pharmacokinetic Study of Intermittent Intraperitoneal Vancomycin in Adult Subjects Receiving Automated Peritoneal Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peritoneal Dialysis-associated Peritonitis
Keywords: Vancomycin
Pharmacokinetics
Pharmacodynamics
Automated Peritoneal Dialysis
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2018-09-26
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Total Plasma Concentration (Cmax)
timeFrame: Day: 1
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Day: 1
measure: Area Under the Concentration-time Curve (AUC0-inf)
timeFrame: Days: 1-7
measure: Total Body Clearance (CLtotal)
timeFrame: Days: 1-7
measure: Dialytic Clearance
timeFrame: Days: 1-7
Secondary outcomes:
measure: Adverse Events
timeFrame: Days: 1-7
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Walter K Kraft, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.