Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT04299867 |
Other study ID # |
Pro00103890 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
July 15, 2020 |
Est. completion date |
April 25, 2022 |
Study information
Verified date |
July 2022 |
Source |
Duke University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
This study aims to define the pharmacokinetic (PK) properties of a commonly used antibiotic
to treat cIAI, metronidazole, in the intestinal wall tissue of healthy infants undergoing
intestinal surgery to optimize intestinal wall penetration of antibiotics in infants.
Metronidazole will be given at standard of care intravenous loading dose of 30 mg/kg 15
minutes prior to incision, with a maximum dose of 2g. Intraoperative plasma samples will be
obtained from pre-existing vascular access catheters at end of bolus, 30, 60, 90 minutes, at
time of intestinal excision, and at the end of the case in ethylenediaminetetraacetic acid
microcontainers, exceeding no more than 5mL total.
Description:
This is a single center pilot pharmacokinetic (PK) study to concomitantly measure antibiotic
concentrations in the plasma and the intestinal wall of healthy infants undergoing intestinal
surgery.
Metronidazole will be given at standard of care intravenous loading dose of 30 mg/kg 15
minutes prior to incision, with a maximum dose of 2g. Exact time, dose, and infusion rate and
duration will be recorded. The use of a loading dose will allow characterization of plasma
and tissue PK after a single dose that would be expected with steady state dosing, thus
increasing the translatability of the investigator's findings to cIAI treatment.
Intraoperative plasma samples will be obtained from pre-existing vascular access catheters at
end of bolus, 30, 60, 90 minutes, at time of intestinal excision, and at the end of the case
in ethylenediaminetetraacetic acid microcontainers, exceeding no more than 5mL total. At the
time of intestinal excision, the surgeon will cut at least 250mg of intestine from the
specimen, ensuring all layers of bowel are included. This sample will be placed in a sterile,
dry container. All samples will be processed and stored in a -80°C freezer within 1 hour of
acquisition. Samples will be batched and shipped to a central commercial laboratory (OpAns
Analytical Solutions LLC, Durham, NC) for concentration measurement of metronidazole and its
primary metabolite 2-hydroxymetronidazole using a HPLC/MS/MS plasma assay previously
developed and validated per FDA guidance. This assay will be modified and validated for
tissue concentration measurement utilizing porcine intestinal tissue and run over three
mediums to ensure correct measurement. The samples will also be used to quantify CYP2A6
protein levels using commercially available enzyme-linked immunosorbent assay kits.