NICU Antibiotics and Outcomes (NANO) Follow-up Study

Premature Birth Clinical Trial

— NANO-FU  

Official title:

NICU Antibiotics and Outcomes Follow-Up Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05977400
• Other study ID #: NANO Follow-Up
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2024
• Est. completion date: March 2029

Study information

• Verified date: July 2023
• Source: Sharp HealthCare
• Contact: Anup Katheria, MD
• Phone: 8589394170
• Email: anup.katheria[@]sharp.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 802
• Est. completion date: March 2029
• Est. primary completion date: March 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 30 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Antibiotics
• Neurodevelopment
• Premature Birth

Intervention

Drug:
• Ampicillin
Intravenous Ampicillin
• Gentamicin
Intravenous Gentamicin
• Placebo
Intravenous Normal Saline

Locations

Country	Name	City	State
Canada	Sinai Health System	Toronto
United States	State University of New York Downstate	Brooklyn	New York
United States	The Pennsylvania State University	Hershey	Pennsylvania
United States	University of Louisville	Louisville	Kentucky
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Jefferson Medical College of Thomas Jefferson University	Philadelphia	Pennsylvania
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Magee-Womens Hospital	Pittsburgh	Pennsylvania
United States	The University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Sharp Mary Birch Hospital for Women & Newborns	San Diego	California
United States	University of South Florida	Tampa	Florida
United States	Westchester Medical Center	Valhalla	New York

Sponsors (14)

Lead Sponsor

Collaborator

Sharp HealthCare

Children's Hospital of Philadelphia, Jefferson Medical College of Thomas Jefferson University, Morgan Stanley Children's Hospital, Mount Sinai Hospital, Canada, Penn State University, Sharp Mary Birch Hospital for Women & Newborns, State University of New York - Downstate Medical Center, The University of Texas Health Science Center at San Antonio, University of Louisville, University of Pittsburgh, University of South Florida, Westchester Medical Center, Yale University

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of neurodevelopmental impairment or Death	The first primary outcome will be a composite of newborn or childhood death OR one of following: cognitive or motor composite scores <80 on the Bayley-4, Gross Motor Function Classification Score score =2, bilateral blindness, severe functional hearing impairment. The incidence of the composite outcome will be compared between the placebo and early antibiotic groups.	24 months corrected gestational age
Primary	DOOR probability Distribution	The second primary outcome will be a comparison of the DOOR probability of more desirable outcomes at 2 years using a novel ordinal endpoint scale developed during the trial. Outcomes to be included in the rank are as follows: death, cognitive/language/motor composite scores<80 on the Bayley-4, Gross Motor Function Classification Score =2, bilateral blindness, severe functional hearing impairment, Child Behavior Checklist (CBCL) scores >70, autism risk scores (MCHAT R/F) of =2, and medical measures, such as need for oxygen support. The distribution of the finalized neoDOOR will be compared between the placebo and empiric antibiotic groups.	24 months corrected gestational age