Clinical trial NCT05977400: NICU Antibiotics and Outcomes (NANO) Follow-up Study
Official title: NICU Antibiotics and Outcomes Follow-Up Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Premature Birth
Antibiotics
Neurodevelopment
Lead sponsor: Sharp HealthCare
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
name: Morgan Stanley Children's Hospital
name: University of Louisville
name: Sharp Mary Birch Hospital for Women & Newborns
name: Children's Hospital of Philadelphia
name: Jefferson Medical College of Thomas Jefferson University
name: University of South Florida
name: Westchester Medical Center
name: Yale University
name: The University of Texas Health Science Center at San Antonio
name: Penn State University
name: State University of New York - Downstate Medical Center
name: Mount Sinai Hospital, Canada
First posted: 2023-08-04
Enrollment: 802
Sex: ALL
Minimum age (years): 23
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 outcomes:
measure: Rate of neurodevelopmental impairment or Death
timeFrame: 24 months corrected gestational age
measure: DOOR probability Distribution
timeFrame: 24 months corrected gestational age
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women & Newborns
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Brooklyn
country: United States
facility: State University of New York Downstate
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Hershey
country: United States
facility: The Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Medical College of Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: The University of Pittsburgh Medical Center
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Toronto
country: Canada
facility: Sinai Health System
Study officials:
affiliation: Sharp HealthCare
name: Anup Katheria, MD
role: PRINCIPAL_INVESTIGATOR
References: