NICU Antibiotics and Outcomes (NANO) Follow-up Study

NCT05977400 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: NANO Follow-Up
• Study Type: interventional
• Target: 802
• Locations: 2 countries
• Sites: 15

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.

Conditions

Premature Birth; Antibiotics; Neurodevelopment

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (2)

Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life

ACTIVE COMPARATOR

Neonates in this group will have been enrolled and randomized into the NANO trial and received a blinded 48 hour course of empiric antibiotic treatment.

Drug: Ampicillin; Drug: Gentamicin

Very preterm infants that do not receive empiric antibiotic treatment in the first 48 hours of life

PLACEBO COMPARATOR

Neonates in this group will have been enrolled and randomized into the NANO trial and received a blinded 48 hour course of placebo.

Drug: Placebo

Interventions

Ampicillin DRUG

Intravenous Ampicillin

Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life

Gentamicin DRUG

Intravenous Gentamicin

Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life

Placebo DRUG

Intravenous Normal Saline

Very preterm infants that do not receive empiric antibiotic treatment in the first 48 hours of life

Eligibility Criteria

• Age: 23 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent NANO trial Criteria:

You may not qualify if:

• 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
• 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
• 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
• Infants with ongoing hemodynamic instability requiring vasopressors or more than one fluid bolus at time of randomization
• Clinician concern for sepsis due to physical exam findings or clinical history of mother or infant
• Major congenital anomalies
• Infants not anticipated to survive beyond 72 hours
• Infants who have received antibiotics prior to randomization.

Sponsors & Collaborators

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

Study Sites (15)

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

University of South Florida

Tampa, Florida, 33620, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

State University of New York Downstate

Brooklyn, New York, 11203, United States

Location

Columbia University

New York, New York, 10027, United States

Location

University of Rochester

Rochester, New York, 14611, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

The Pennsylvania State University

Hershey, Pennsylvania, 17033-0850, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Jefferson Medical College of Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

The University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Sinai Health System

Toronto, Canada

Location

MeSH Terms

Conditions

Premature Birth

Interventions

Ampicillin; Gentamicins

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Anup Katheria, MD

  Sharp HealthCare

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anup Katheria, MD

CONTACT

8589394170; anup.katheria@sharp.com

Rebecca Dorner, MD

CONTACT

rebecca.dorner@sharp.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: August 4, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: August 4, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: 2 years after primary publication
• Access Criteria: An archived dataset with documentation will be made available for additional uses by outside investigators, in collaboration with the study investigators. We will work with NICHD program staff to develop a broad data sharing plan over time.

Locations

CA (1); US (14)