Peritoneal Dialysis-associated Peritonitis
Conditions
Keywords
Vancomycin, Pharmacokinetics, Pharmacodynamics, Automated Peritoneal Dialysis
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.
Interventions
DRUGVancomycin
Vancomycin one-time 20 mg/kg intraperitoneal dose.
Sponsors
Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Total Plasma Concentration (Cmax) | Day: 1 | Total systemic plasma concentration following 12-hour dwell |
| Time to Maximum Plasma Concentration (Tmax) | Day: 1 | Time (hours) to achieve the maximum plasma concentration |
| Area Under the Concentration-time Curve (AUC0-inf) | Days: 1-7 | AUC based on vancomycin plasma concentrations |
| Total Body Clearance (CLtotal) | Days: 1-7 | Total vancomycin plasma vancomycin clearance |
| Dialytic Clearance | Days: 1-7 | Vancomycin clearance from peritoneal dialysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Days: 1-7 | Any adverse events throughout entirety of study as assessed by physician-investigator |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Vancomycin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 43 years STANDARD_DEVIATION 19 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Area Under the Concentration-time Curve (AUC0-inf)
AUC based on vancomycin plasma concentrations
Time frame: Days: 1-7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vancomycin | Area Under the Concentration-time Curve (AUC0-inf) | 2589.9 hr x mg/L | Standard Deviation 365.6 |
Primary
Dialytic Clearance
Vancomycin clearance from peritoneal dialysis
Time frame: Days: 1-7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vancomycin | Dialytic Clearance | 11.1 mL/min | Standard Deviation 4.3 |
Primary
Maximum Total Plasma Concentration (Cmax)
Total systemic plasma concentration following 12-hour dwell
Time frame: Day: 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vancomycin | Maximum Total Plasma Concentration (Cmax) | 28.7 mg/L | Standard Deviation 4.9 |
Primary
Time to Maximum Plasma Concentration (Tmax)
Time (hours) to achieve the maximum plasma concentration
Time frame: Day: 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vancomycin | Time to Maximum Plasma Concentration (Tmax) | 14.4 hours |
Primary
Total Body Clearance (CLtotal)
Total vancomycin plasma vancomycin clearance
Time frame: Days: 1-7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vancomycin | Total Body Clearance (CLtotal) | 7.2 mL/min | Standard Deviation 1.3 |
Secondary
Adverse Events
Any adverse events throughout entirety of study as assessed by physician-investigator
Time frame: Days: 1-7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vancomycin | Adverse Events | 0 Participants |