Perioperative Tissue Penetration of Antimicrobials in Infants

NCT04299867 | Completed

• 1 other identifier: Pro00103890
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bowel Dysfunction

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic Clearance

  Day of Surgery + 12 hours

• Pharmacokinetic Half-life

  Day of Surgery + 12 hours

• Pharmacokinetic Volume of Distribution

  Day of Surgery + 12 hours

• Pharmacokinetic Area under the curve

  Day of Surgery + 12 hours

Secondary Outcomes (4)

• CYP2A6 quantification

  Day of Surgery + 12 hours

• Ratio of Metronidazole to 2-hydroxymetronidazole concentration

  Day of Surgery + 3-4 hours

• Mean Plasma Concentration of Metronidazole

  Day of Surgery + 3-4 hours

• Mean Plasma Concentration of 2-hydroxymetronidazole

  Day of Surgery + 3-4 hours

Study Arms (2)

< 34 weeks gestational age

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.

Procedure: Bowel Surgery with Metronidazole

34 weeks gestational age

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.

Procedure: Bowel Surgery with Metronidazole

Interventions

Bowel Surgery with Metronidazole PROCEDURE

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.

34 weeks gestational age; < 34 weeks gestational age

Eligibility Criteria

• Age: 0 Years - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Children \< 2 years of age undergoing intestinal surgery

You may qualify if:

• Age 0 to 2 years at enrollment
• Written informed consent provided by a parent or legal guardian
• Scheduled to undergo elective intestinal operation for the removal of non-infected bowel
• Sufficient intravascular access to complete the study procedures

You may not qualify if:

• Prior treatment with metronidazole for any dose during the 72 hours prior to study drug administration.
• Patients with active inflammatory or infectious conditions of the bowel such as inflammatory bowel disease, Hirschprung's disease in the portion of bowel to be excised, diverticular disease, cancerous or pre-cancerous lesions, colitis, enteritis, ulcerative disease, Meckel's diverticulum, celiac disease, and irritable bowel syndrome.
• Renal dysfunction defined as serum creatinine \>2 mg/dL at enrollment
• Receiving any extracorporeal life support including extracorporeal membrane oxygenation, ventricular assist devices, and renal replacement therapy at enrollment
• Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the participant or the quality of the data.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples Intestinal tissue

MeSH Terms

Conditions

Intestinal Diseases

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christoph Hornik, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 9, 2020
• Study Start: July 15, 2020
• Primary Completion: March 26, 2022
• Study Completion: April 25, 2022
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)