Pharmacokinetics of Preoperative Vancomycin

Preoperative Vancomycin Administration for Surgical Site Prophylaxis: Plasma and Soft Tissue Concentrations in Pediatric Neurosurgical and Orthopedic Patients

A study of plasma and tissue vancomycin pharmacokinetics in pediatric surgical patients.

Study Overview

• Status: Completed
• Conditions: Surgical Site Infection; Vancomycin
• Intervention / Treatment: Drug: Administration of Vancomycin

Detailed Description

Background: Vancomycin is used for antibiotic prophylaxis in pediatric surgical patients without a complete understanding of plasma and soft tissue pharmacokinetics. Guidelines recommend incision within 60 minutes after administration; however, tissue concentrations of vancomycin at that early time may not be therapeutic. The Investigators conducted a study of plasma and tissue concentrations in pediatric neurosurgical and orthopedic patients to characterize intraoperative vancomycin pharmacokinetics.

Patients, ages (0.1-18.8 years), undergoing posterior spinal fusion (n=30) or ventriculoperitoneal shunt placement (n=30), received intravenous vancomycin 15 mg/kg over one hour. Skin biopsies were taken at incision and skin closure. Blood samples were also collected at incision and closure; additional samples were drawn at 2- and 4-hours if patient was still in surgery. Population pharmacokinetic (PK) analysis was performed to characterize PK parameter estimates and to develop a model of intraoperative plasma and tissue vancomycin concentrations vs. time.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Neurosurgery patients between the ages of 31 days up to 18 years
2. Receiving a single dose of vancomycin administered prior to surgery for cerebrospinal fluid (CSF) shunt placement or revision.
3. Orthopedic surgical patients between the ages of 31 days up to 18 years
4. Receiving a single dose of vancomycin administered prior to surgery for definitive spinal fusion.

Exclusion Criteria:

1. Patients already receiving vancomycin for treatment of an active infection,
2. Patients who have a Creatinine ≥1.2,
3. Patients who's creatinine clearance less than 50,
4. Known chronic renal failure and are on dialysis,
5. Patients with a known allergy to vancomycin, not including Red Man Syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Administration of Vancomycin; Administration of Vancomycin 15 mg/kg over 1 hour prior to surgical incision	Drug: Administration of Vancomycin; Intravenous Vancomycin Administration; Other Names: Vancomycin Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics Analysis: V˅c	Volume of the central compartment. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Pharmacokinetics Analysis: V˅2	Volume of the peripheral compartment Typical value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Pharmacokinetics Analysis: Q	Intercompartmental clearance between central compartment (Vc) and peripheral compartment (V2) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Pharmacokinetics Analysis: Cle	Elimination clearance. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Pharmacokinetics Analysis: sf˅V2	Scaling Factor for Body weight covariate for V2 (Volume of the peripheral compartment) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Pharmacokinetics Analysis: sf˅Cle	Scaling Factor for Body weight covariate for Cle (elimination clearance) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Pharmacokinetics Analysis: K˅skin0	Accounts for the equilibration rate between plasma and skin. Typical Value should be read as 3.6E-05. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Pharmacokinetics Analysis: PC	Partition coefficient, models skin drug concentration between plasma and skin. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Pharmacokinetics Analysis: δ ˅R-plasma	Proportional or relative intrasubject variability for plasma data Typical Value. There is no unit of measure for this measurement. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Pharmacokinetics Analysis: δ ˅A-skin	Additive intrasubject variability for skin data Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.	1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Melissa Brooks-Peterson, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2012
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): July 20, 2015

Study Registration Dates

• First Submitted: February 14, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (ACTUAL): March 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Wound Infection; Surgical Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: 12-1411

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No