Ignite Creation Date:
2025-12-25 @ 12:43 AM
Ignite Modification Date:
2025-12-25 @ 10:55 PM
Study NCT ID:
NCT04299867
Status:
COMPLETED
Last Update Posted:
2025-11-10
First Post:
2020-03-05
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Perioperative Tissue Penetration of Antimicrobials in Infants
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007410', 'term': 'Intestinal Diseases'}], 'ancestors': [{'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008795', 'term': 'Metronidazole'}], 'ancestors': [{'id': 'D009593', 'term': 'Nitroimidazoles'}, {'id': 'D009574', 'term': 'Nitro Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2022-03-08', 'size': 756237, 'label': 'Study Protocol, Statistical Analysis Plan, and Informed Consent Form', 'hasIcf': True, 'hasSap': True, 'filename': 'Prot_SAP_ICF_000.pdf', 'typeAbbrev': 'Prot_SAP_ICF', 'uploadDate': '2023-06-23T15:09', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Plasma samples Intestinal tissue'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 21}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-07-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-11', 'completionDateStruct': {'date': '2022-04-25', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-11-07', 'studyFirstSubmitDate': '2020-03-05', 'studyFirstSubmitQcDate': '2020-03-06', 'lastUpdatePostDateStruct': {'date': '2025-11-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2020-03-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-03-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Pharmacokinetic Clearance', 'timeFrame': 'Day of Surgery + 12 hours'}, {'measure': 'Pharmacokinetic Half-life', 'timeFrame': 'Day of Surgery + 12 hours'}, {'measure': 'Pharmacokinetic Volume of Distribution', 'timeFrame': 'Day of Surgery + 12 hours'}, {'measure': 'Pharmacokinetic Area under the curve', 'timeFrame': 'Day of Surgery + 12 hours'}], 'secondaryOutcomes': [{'measure': 'CYP2A6 quantification', 'timeFrame': 'Day of Surgery + 12 hours'}, {'measure': 'Ratio of Metronidazole to 2-hydroxymetronidazole concentration', 'timeFrame': 'Day of Surgery + 3-4 hours'}, {'measure': 'Mean Plasma Concentration of Metronidazole', 'timeFrame': 'Day of Surgery + 3-4 hours'}, {'measure': 'Mean Plasma Concentration of 2-hydroxymetronidazole', 'timeFrame': 'Day of Surgery + 3-4 hours'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Bowel Dysfunction']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nMetronidazole 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.\n\nIntraoperative 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '2 Years', 'minimumAge': '0 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Children \\< 2 years of age undergoing intestinal surgery', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Age 0 to 2 years at enrollment\n2. Written informed consent provided by a parent or legal guardian\n3. Scheduled to undergo elective intestinal operation for the removal of non-infected bowel\n4. Sufficient intravascular access to complete the study procedures\n\nExclusion Criteria:\n\n1. Prior treatment with metronidazole for any dose during the 72 hours prior to study drug administration.\n2. 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.\n3. Renal dysfunction defined as serum creatinine \\>2 mg/dL at enrollment\n4. Receiving any extracorporeal life support including extracorporeal membrane oxygenation, ventricular assist devices, and renal replacement therapy at enrollment\n5. Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the participant or the quality of the data."}, 'identificationModule': {'nctId': 'NCT04299867', 'briefTitle': 'Perioperative Tissue Penetration of Antimicrobials in Infants', 'organization': {'class': 'OTHER', 'fullName': 'Duke University'}, 'officialTitle': 'Perioperative Tissue Penetration of Antimicrobials in Infants', 'orgStudyIdInfo': {'id': 'Pro00103890'}}, 'armsInterventionsModule': {'armGroups': [{'label': '< 34 weeks gestational age', 'description': '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.\n\nAt 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.', 'interventionNames': ['Procedure: Bowel Surgery with Metronidazole']}, {'label': '34 weeks gestational age', 'description': '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.\n\nAt 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.', 'interventionNames': ['Procedure: Bowel Surgery with Metronidazole']}], 'interventions': [{'name': 'Bowel Surgery with Metronidazole', 'type': 'PROCEDURE', 'description': '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.\n\nAt 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.', 'armGroupLabels': ['34 weeks gestational age', '< 34 weeks gestational age']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27710', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University Health System', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}], 'overallOfficials': [{'name': 'Christoph Hornik, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Duke University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Aggregate data and results will be shared in publication'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Duke University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}