NCT04299867

Perioperative Tissue Penetration of Antimicrobials in Infants

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 21 (actual)
• Sponsor: Duke University · Academic / Other
• Sex: All
• Age: 0 Years – 2 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Bowel Dysfunction

Interventions

Type	Name	Description
PROCEDURE	Bowel Surgery with Metronidazole	Metronidazole will be given per standard of care prior to incision. 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(s), and at the end of the case in ethylenediaminetetraacetic acid microcontainers, exceeding no more than approximately 5 mL total. At the time of intestinal excision, the surgeon will cut at least 500 mg of intestine from the specimen, ensuring all layers of bowel are included. If more than one intestinal sample is taken during the surgery, such as in the case of multiple strictures removed, each sample will be obtained and labeled appropriately.

Timeline

• Start date: 2020-07-15
• Primary completion: 2022-03-26
• Completion: 2022-04-25
• First posted: 2020-03-09
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States