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CompletedNCT03453684Updated May 24, 2022Results posted

Pharmacokinetics of Preoperative Vancomycin

A Phase 4 interventional study of Administration of Vancomycin in Surgical Site Infection and Vancomycin, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 31 Days to 18 Years. Per ClinicalTrials.gov, last updated 2022-05-24.

Sponsored by University of Colorado, Denver · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
60
Allocation
Not applicable
Ages
31 Days to 18 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Surgical Site Infection
  • Vancomycin
03

Who can participate

Ages eligible
31 Days to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    Administration of Vancomycin

    Administration of Vancomycin 15 mg/kg over 1 hour prior to surgical incision

    Drug: Administration of Vancomycin

Interventions

  • DrugAdministration of Vancomycin

    Intravenous Vancomycin Administration

    Also known as: Vancomycin Hydrochloride

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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).

  2. 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.

    Time frame: 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).

  3. 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.

    Time frame: 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).

  4. 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.

    Time frame: 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).

  5. 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.

    Time frame: 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).

  6. 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.

    Time frame: 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).

  7. 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.

    Time frame: 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)

  8. 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.

    Time frame: 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)

  9. 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.

    Time frame: 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)

  10. 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.

    Time frame: 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)

06

Results

Posted May 24, 2022
Limitations and caveats
Outcome measures were determined by complex mathematical modeling utilizing the pharmacokinetics estimates listed above. Outcome measures are described as necessary report the pharmacokinetic data. Outcome measures reflect the study protocol.

Participant flow

30 patients scheduled to undergo posterior spinal fusion 30 patients scheduled to undergo ventriculo-peritoneal (VP) shunt placement

Participant flow — Overall Study
MilestoneAdministration of Vancomycin
Started60
Completed60
Not completed0

Outcome measures

PrimaryPharmacokinetics 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.

Time frame:
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).
Reported as:
Number · L
Pharmacokinetics Analysis: V˅c
LAdministration of Vancomycin
Typical value2.56
w^21.14
Statistical analysis
  • Administration of Vancomycin · Overall se of the estimate: 0.009Standard error of the estimate of Typical value: 0.45 Standard error of the estimate of w\^2: 0.39
PrimaryPharmacokinetics 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.

Time frame:
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).
Reported as:
Number · L/35kg
Pharmacokinetics Analysis: V˅2
L/35kgAdministration of Vancomycin
Pharmacokinetics Analysis: V˅25.30
Statistical analysis
  • Administration of Vancomycin · Overall standard error of the estimate: 9.85Standard error of the estimate of Typical value: 0.61 Standard error of the estimate of ꙍ\^2 (intersubject variability): \^a (fixed to 0)
PrimaryPharmacokinetics 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.

Time frame:
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).
Reported as:
Number · L/min
Pharmacokinetics Analysis: Q
L/minAdministration of Vancomycin
Pharmacokinetics Analysis: Q0.12
Statistical analysis
  • Administration of Vancomycin · Overall standard error of the estimate: 8.37Standard error of the estimate of Typical value: 0.02 Standard error of the estimate of ꙍ\^2 (intersubject variability): \^a (fixed to 0)
PrimaryPharmacokinetics 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.

Time frame:
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).
Reported as:
Number · L/min/1.73 m^2
Pharmacokinetics Analysis: Cle
L/min/1.73 m^2Administration of Vancomycin
Typical value0.09
ꙍ^2 (Intersubject variability)0.13
Statistical analysis
  • Administration of Vancomycin · Overall standard error of the estimate: 4.83Standard error of the estimate of Typical value: 0.003 Standard error of the estimate of ꙍ\^2 (intersubject variability): 0.03
PrimaryPharmacokinetics 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.

Time frame:
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).
Reported as:
Number · L/35kg
Pharmacokinetics Analysis: sf˅V2
L/35kgAdministration of Vancomycin
Pharmacokinetics Analysis: sf˅V21.01
Statistical analysis
  • Administration of Vancomycin · Overall standard error of the estimate: 17.21Standard error of the estimate of Typical value: 0.13
PrimaryPharmacokinetics 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.

Time frame:
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).
Reported as:
Number · L/min/1.73m^2
Pharmacokinetics Analysis: sf˅Cle
L/min/1.73m^2Administration of Vancomycin
Pharmacokinetics Analysis: sf˅Cle1.69
Statistical analysis
  • Administration of Vancomycin · Se of the estimate of typical value: 0.20
PrimaryPharmacokinetics 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.

Time frame:
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)
Reported as:
Number · min^-1
Pharmacokinetics Analysis: K˅skin0
min^-1Administration of Vancomycin
Typical value3.6
ꙍ^2 (Intersubject variability)2.0
Statistical analysis
  • Administration of Vancomycin · Se of the estimate of typical value: 2.1Standard error of the estimate of Typical value should be read as: 2.1E-06 Standard error of the estimate of ꙍ\^2 (intersubject variability): 0.24
PrimaryPharmacokinetics 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.

Time frame:
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)
Reported as:
Number · Coefficient
Pharmacokinetics Analysis: PC
CoefficientAdministration of Vancomycin
Typical value32.0
ꙍ^2 (Intersubject variability)3.7
Statistical analysis
  • Administration of Vancomycin · Se of the estimate of typical value: 2.3Standard error of the estimate of ꙍ\^2 (intersubject variability): 0.08
PrimaryPharmacokinetics 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.

Time frame:
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)
Reported as:
Number · No unit of measure
Pharmacokinetics Analysis: δ ˅R-plasma
No unit of measureAdministration of Vancomycin
Pharmacokinetics Analysis: δ ˅R-plasma0.23
Statistical analysis
  • Administration of Vancomycin · Overall standard error of the estimate: 10.80Standard error of the estimate of Typical value: 0.02
PrimaryPharmacokinetics 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.

Time frame:
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)
Reported as:
Number · μg
Pharmacokinetics Analysis: δ ˅A-skin
μgAdministration of Vancomycin
Pharmacokinetics Analysis: δ ˅A-skin7.5
Statistical analysis
  • Administration of Vancomycin · Se of the estimate of typical value: 0.90

Adverse events

Collected over 1 day. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Administration of Vancomycin0/59 (0%)0/59 (0%)0/59 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Administration of Vancomycin
<=18 years57
Between 18 and 65 years2
>=65 years0
Age, Continuous
Age, Continuous(years)Administration of Vancomycin
Mean7.8 ± 5.9
Sex: Female, Male
Sex: Female, Male(Participants)Administration of Vancomycin
Female37
Male22
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Administration of Vancomycin
07

Study locations

1 site
  • University of Colorado Anschutz Medical Campus
    Aurora, Colorado 80045, United States
08

Registry details

Key details

Study ID
NCT03453684
Lead sponsor
University of Colorado, Denver
Responsible party
Sponsor
First posted
Mar 5, 2018
Start date
Dec 1, 2012
Primary completion
Jun 2013
Completion
Jul 20, 2015
Results posted
May 24, 2022
Last update
May 24, 2022

Study contacts

Melissa Brooks-Peterson, MD
principal investigator · University of Colorado, Denver

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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