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ClinicalTrials.gov ID

NCT05977400

Lead Sponsor

Sharp HealthCareOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

802Estimated

Last Update Posted

Aug 4, 2023Actual

Start Date

Apr 2024Estimated

Primary Completion Date

Mar 2029Estimated

Completion Date

Mar 2029Estimated

Official Title

NICU Antibiotics and Outcomes Follow-Up Study

Brief Summary

The NANO follow-up study is designed to determine whether a simple, cost-effective intervention- withholding antibiotics at birth- reduces clinically relevant outcomes such as behavioral and neurological impairment at 2 years of age. This study will be the largest study evaluating the effects of early antibiotics in children with comprehensive measures of neurodevelopment linked to genomic variants and microbiota interactions.

Detailed Description

The multidisciplinary team launched the NANO (NICU Antibiotics and Outcomes) Trial to study the longstanding clinical practice of empirically administering intravenous antibiotics to very preterm infants. The NANO trial is an 802-patient,13-site randomized blinded controlled trial (R01HD09757801) discerning whether administration of antibiotics within the first three days of life increases the incidence of short-term, life-threatening complications among very preterm infants.

The proposed NANO follow-up study will build upon the parent NANO trial to determine whether avoiding antibiotics in very preterm infants - a simple, cost-effective intervention - improves neurodevelopmental and behavioral outcomes during the toddler years. Evaluation of children enrolled in the proposed NANO follow-up study will include serial comprehensive, standardized assessments of motor, cognitive, behavioral and adaptive outcomes. To support retention and provide an important early assessment, a first virtual visit at 1 year of age will include the Hammersmith Infant Neurologic Exam (HINE) and the Developmental Assessment of Young Children, Second Edition (DAYC-2). A second comprehensive follow-up visit in person at 2 years will include the Bayley Scales of Infant Development 4th ed., Gross Motor Function Classification System, Child Behavior Checklist for ages 1.5-5, and the Modified Checklist for Autism in Toddlers, Revised, with Follow-up.

In the NANO follow-up trial, outcomes will be assessed using the Desirability of outcome ranking (DOOR), an innovative, patient-centered statistical approach used in clinical trials to evaluate the global benefits and risks of an intervention. The ordinal neonatal follow-up endpoint composite scale, to be named neoDOOR, will be developed by both clinicians and families. Stakeholder meetings will develop consensus rankings of individual and composite outcomes of different severities reported by the above developmental assessments. Neonatal biospecimens collected during the parent NANO trial will allow for additional exploratory analyses evaluating interactions among genetics, environment, and microbiota with antibiotic exposure and long-term outcomes. Through these assessments and evaluation, the investigators will provide substantial evidence for the use (or non-use) of early antibiotics for very preterm infants at birth.

• Premature Birth
• Antibiotics
• Neurodevelopment

• Ampicillin
• Gentamicin
• Placebo

Ages Eligible for Study

Child (0-17)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Families that have agreed to participate and are enrolled in the parent NANO trial will be eligible for the NANO follow-up study. There will be no exclusions for eligible children entering the follow-up study.

Parent NANO trial Criteria:

I. Inclusion criteria: We will enroll newborn infants with gestational age of 23.0-30.6 weeks born to mothers 18 years or older at participating study sites. Only inborn infants at participating study sites will be eligible.

II. Exclusion criteria:

1. Infants at low risk for early onset sepsis-Infants born for maternal indications via caesarean section with rupture of membranes within 6 hours, without attempts to induce labor, and without concern for maternal infection
2. Infants at high risk for early onset sepsis- Infants born to mothers with intrapartum fever (> 38ºC) or clinical diagnosis of chorioamnionitis (suspected or definite), infants born to mothers with proven Group B Streptococcus colonization or indication for intrapartum antibiotic prophylaxis that did not receive adequate antibiotic treatment according to specialty specific guidelines, (i.e., penicillin, ampicillin, cefazolin), infant born to mother with previous infant with GBS disease/infection
3. Infants with respiratory insufficiency requiring invasive mechanical ventilation and fraction of inspired oxygen> 0.40 or non-invasive ventilation and fraction of inspired oxygen > 0.60 at time of randomization
4. Infants with ongoing hemodynamic instability requiring vasopressors or more than one fluid bolus at time of randomization
5. Clinician concern for sepsis due to physical exam findings or clinical history of mother or infant
6. Major congenital anomalies
7. Infants not anticipated to survive beyond 72 hours
8. Infants who have received antibiotics prior to randomization.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Quadruple

Lead Sponsor

Sharp HealthCareOTHER

Collaborators

University of PittsburghOTHER

Morgan Stanley Children's HospitalOTHER

University of LouisvilleOTHER

Sharp Mary Birch Hospital for Women & NewbornsOTHER

Children's Hospital of PhiladelphiaOTHER

Jefferson Medical College of Thomas Jefferson UniversityOTHER

University of South FloridaOTHER

Westchester Medical CenterOTHER

Yale UniversityOTHER

The University of Texas Health Science Center at San AntonioOTHER

Penn State UniversityOTHER

State University of New York - Downstate Medical CenterOTHER

Mount Sinai Hospital, CanadaOTHER

angela.montgomery@yale.edu

rap32@cumc.columbia.edu

Ashraf.Kharrat@sinaihealth.ca