Optimizing PreTerm Infant Ampicillin Dosing (OPTI-Amp)

An Open-label, Pharmacokinetic and Safety Trial Optimizing PreTerm Infant Ampicillin Dosing

The goal of this clinical trial is to learn if preterm infants who are prescribed antibiotics shortly after birth can safety receive a shorter course of antibiotics (24 to 36 hours instead of 48 hours). The main questions it aims to answer are:

• Does short-course ampicillin provide high enough levels of ampicillin at 48 hours?
• Is short-course ampicillin safe for preterm infants to receive?

Preterm infants who are being prescribed ampicillin by their doctor and enroll in the study will stop ampicillin after a shorter than typical course, and researchers will collect blood samples to measure their ampicillin levels and follow them clinically to see how they do after receiving short-course ampicillin.

Participants will:

• stop ampicillin earlier than 48 hours (between 24 to 36 hours, depending on how premature they are and the dosing of ampicillin their doctor has prescribed)
• have a blood sample collected around 48 hours from when they started ampicillin
• have their data collected until 30 days after they receive short-course ampicillin, or until hospital discharge, whichever is sooner

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm Neonates; NICU; Safety and Pharmacokinetics; Ampicillin; Early Onset Sepsis
• Intervention / Treatment: Drug: Ampicillin prescribed by provider per standard of care for evaluation of early onset sepsis

Detailed Description

OPTI-Amp is a prospective, open-label, non-randomized pharmacokinetic and safety trial of short-course ampicillin administered to preterm neonates in the Neonatal Intensive Care Unit (NICU) at Duke.

The objectives of the study are to 1) evaluate whether short-course ampicillin provides therapeutic exposures for 48 hours from ampicillin initiation for preterm neonates undergoing evaluation of early onset sepsis (EOS) and 2) evaluate the safety of short-course ampicillin compared to standard empiric ampicillin. The prescribing of drugs to infants will not be part of this protocol.

Approximately 60 neonates ≤34 weeks gestational age and <7 days postnatal age at the time of screening, who are receiving empiric ampicillin prescribed per standard of care (SOC) by their treating provider will be enrolled in the study. Participants will be in the study up to 30 days or hospital discharge, whichever is sooner. Enrolled infants who receive short-course ampicillin will have a pharmacokinetic sample collected at 48 (+/-2) hours from the time that ampicillin was initiated. Additional opportunistic pharmacokinetic (PK) samples can be collected between the final ampicillin dose (time of enrollment) and 72 hours from ampicillin initiation if the patient is receiving other SOC labs; however, these are not required. Demographic information, clinical data, and biospecimen information (including date and time of sample collection) will also be collected for enrolled participants.

All enrolled infants will be in the safety population. Those with at least one PK sample will be included in the PK population. In addition to the risks of blood drawing and loss of confidentiality, there may be a risk of under treatment of EOS if clinical cultures result positive after ampicillin discontinuation and therapeutic exposure is not maintained between 24 or 36 hours until 48 hours. Participants that fall under the latter situation will either not be enrolled in the study or will be withdrawn as determined by the study PI.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Angelique Boutzoukas, MD, MPH; Phone Number: 919-668-4733; Email: angelique.boutzoukas@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Health Neonatal Intensive Care Unit
      • Contact: Angelique Boutzoukas, MD, MPH; Phone Number: 919-668-4733; Email: angelique.boutzoukas@duke.edu
      • Contact: Stefany Olague, MPH; Email: smalltrials-CRC@duke.edu
      • Principal Investigator: Angelique Boutzoukas, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented informed consent from parent/guardian
• Infants admitted to the Duke Neonatal Intensive Care Unit (NICU)
• less than or equal to 34 completed weeks gestational age (GA) at birth and < 7 days of life at time of screening
• Prescribed ampicillin by provider per standard of care for evaluation of early onset sepsis

Exclusion Criteria:

• Infant on extracorporeal support (e.g., ECMO)
• Positive blood culture or other confirmed infection
• At time of consent, infants with GA <28 completed weeks who have received more than 24 hours of empiric ampicillin OR infants with GA 28 to 34 completed weeks who have received > 32 to 36 hours of ampicillin, depending on dosing regimen
• Has major congenital abnormalities where survival to 30 days of life is not expected
• Failure to obtain consent from parent/guardian
• Receives a course of ampicillin that is longer (i.e., more doses) than the short-course defined regimen for their GA
• Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short-course Ampicillin; Infants enrolled in the trial receive short-course empiric ampicillin (24 to 36 hours, depending on gestational age and prescribed dosing regimen), rather than a standard (48 hour) empiric ampicillin course	Drug: Ampicillin prescribed by provider per standard of care for evaluation of early onset sepsis; preterm infants receive less than 48 hours of prescribed ampicillin (i.e., a "short-course" ampicillin regimen) to provide the desired 48 hours of therapeutic exposures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free plasma ampicillin concentration	Free plasma ampicillin concentration at 48(+/-) 2 hours after ampicillin initiation, following a single gestational age defined short-course with no further ampicillin administration. Target attainment defined as free ampicillin concentration of ≥1 µg/mL. The short-course regimen is considered successful if target attainment is achieved in ≥90% of the overall study population.	data will be collected up to 50 hours from the first dose of ampicillin

Secondary Outcome Measures

Outcome Measure	Time Frame
Serious, unexpected, suspected adverse reactions to ampicillin	Data will be collected until 30 days from short-course ampicillin, or until hospital discharge
Adverse events related to study procedures	Data will be collected until 30 days from short-course ampicillin, or until hospital discharge
All-cause mortality at 30 days	Data will be collected until 30 days from short-course ampicillin, or until hospital discharge
Antibiotic re-initiation within 7 days of short-course ampicillin	Data will be collected until 7 days from short-course ampicillin
Culture-confirmed bacteremia within 7 days of short-course ampicillin	Data will be collected until 7 days from short-course ampicillin
Necrotizing enterocolitis within 30 days of short-course ampicillin	Data will be collected until 30 days from short-course ampicillin, or until hospital discharge

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: Pro00119855; 1K23HD113839 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD collected for study purposes will be shared to the NICHD DASH data repository.
• IPD Sharing Time Frame: The IPD and supporting information will be available once data analysis is complete and will be available per NICHD DASH repository timelines.
• IPD Sharing Access Criteria: Qualified researchers and scientists from academic, non-profit, and for-profit institutions can access data sent to NICHD DASH repository for secondary analysis. Access is controlled, requiring approval from the DASH Data Access Committee (DAC) after the investigator submits a research proposal, a data use agreement (DUA), and a study-specific Data Management and Sharing Plan.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No