NICU Antibiotics and Outcomes Trial

NCT03997266 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: STUDY20110298R01HD097578
• Study Type: interventional
• Target: 359
• Locations: 1 country
• Sites: 14

Brief Summary

The goal of the NANO trial is to study the longstanding clinical practice of empirically administering intravenous antibiotics to extremely low birthweight (ELBW) infants in the first days of life. In this 802-subject multicenter placebo-controlled randomized clinical trial, the hypothesis to be tested is that the incidence of adverse outcomes is higher in babies receiving empiric antibiotics (EA) in the first week of life compared to babies receiving placebo. The study targets a population of ELBW infants in whom the clinical decision to use or not use EA is currently most challenging -- infants that are clinically stable that did not have a known exposure to intraamniotic infection and were not born preterm for maternal indications. The primary outcome is the composite outcome of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death during the index hospitalization. Secondary safety outcomes will include total antibiotic days, days to full enteral feedings, and common morbidities in preterm infants that have previously been linked to EA, e.g. retinopathy of prematurity and bronchopulmonary dysplasia. Weight and length z-score, and head circumference, are standard measures to be collected weekly by clinical team per a standardized protocol.

Conditions

Extreme Prematurity; Early-Onset Neonatal Sepsis; Late-Onset Neonatal Sepsis; Death; Neonatal; Necrotizing Enterocolitis of Newborn; Microbial Colonization

Keywords

premature birth; human microbiome; antibiotics

Outcome Measures

Primary Outcomes (1)

• Composite incidence of NEC, LOS, or death

  NEC will be assessed by clinical presentation and an abdominal x-ray obtained and read by a certified radiologist. NEC will be defined strictly by Bell's stage II or III criteria for moderate or advanced NEC. To reduce overlap between NEC and diagnosis of spontaneous intestinal perforation, the diagnosis of NEC will only be considered in infants \> 7 days of age. LOS is defined as defined as a positive blood culture obtained after 72 hours of life and intent to treat with antibiotics for 5 days or more. Death is defined as death during the index hospitalization.

  From the time and day of randomization through the subject's date of death from any cause or discharge from the birth hospital, whichever comes first, assessed up until 50 weeks.

Secondary Outcomes (3)

• NEC

  From the time and day of randomization through the subject's date of death from any cause or discharge from the birth hospital, whichever comes first, assessed up until 50 weeks.

• LOS

  From the time and day of randomization through the subject's date of death from any cause or discharge from the birth hospital, whichever comes first, assessed up until 50 weeks.

• Death

  From the time and day of randomization through the subject's date of death from any cause or discharge from the birth hospital, whichever comes first, assessed up until 50 weeks.

Other Outcomes (1)

• Microbial diversity within infant fecal samples

  Weekly stool samples will be collected for the first 8 weeks of life and then monthly through death or discharge from the subject's birth hospital , assessed up to 50 weeks.

Study Arms (2)

Empiric antibiotics

ACTIVE COMPARATOR

Infants will receive standard antibiotic coverage of ampicillin and gentamycin at site approved dosing guidelines while completing an evaluation for early-onset neonatal sepsis.

Drug: Ampicillin; Drug: Gentamycin

Placebo

PLACEBO COMPARATOR

Infants will receive a volume matched placebo of normal saline while completing an evaluation for early-onset neonatal sepsis.

Drug: Normal saline

Interventions

Ampicillin DRUG

Intravenous ampicillin

Empiric antibiotics

Gentamycin DRUG

Intravenous gentamycin

Empiric antibiotics

Normal saline DRUG

Intravenous normal saline

Placebo

Eligibility Criteria

• Age: Up to 4 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Infants born for maternal indications via caesarean section with rupture of membranes at delivery, without attempts to induce labor, and without concern for maternal infection
• Infants at high risk of EOS
• Infants born to mothers with intrapartum fever (\> 38C) or clinical diagnosis of chorioamnionitis
• Infants born to mothers with previous infant with GBS disease/infection
• Infants with respiratory insufficiency requiring invasive mechanical ventilation and FiO2 \> 0.40 or non-invasive ventilation and FiO2 \> 0.60 at time of randomization
• Infants with ongoing hemodynamic instability requiring vasopressors or fluid boluses at time of randomization
• Clinician concern infant is at high risk for sepsis due to infant 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
• Mothers that are \<18 years old at time of enrollment

Sponsors & Collaborators

• Michael Morowitz: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (14)

USA Children's and Women's Hospital

Mobile, Alabama, 36688, United States

Location

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520-8064, United States

Location

University of South Flordia Health

Tampa, Florida, 33606, United States

Location

University of Louisville Research Foundation Inc./Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

The Trustees of Columbia University in the City of New York

New York, New York, 10032-3702, United States

Location

Golisano Children's Hospital at University of Rochester

Rochester, New York, 14642, United States

Location

Maria Fareri Children's Hospital at Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

Location

Penn State Medical College

Hershey, Pennsylvania, 17033, United States

Location

Pennsylvania Hospital/The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Alfred I. duPont for Children of the Nemours Foundation

Philadelphia, Pennsylvania, 19107, United States

Location

Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Morowitz MJ, Katheria AC, Polin RA, Pace E, Huang DT, Chang CH, Yabes JG. The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants. Trials. 2022 May 23;23(1):428. doi: 10.1186/s13063-022-06352-3.

  PMID: 35606829 DERIVED

MeSH Terms

Conditions

Communicable Diseases; Neonatal Sepsis; Perinatal Death; Premature Birth

Interventions

Ampicillin; Gentamicins; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sepsis; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Death; Obstetric Labor, Premature; Obstetric Labor Complications

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 2, 2019
• First Posted: June 25, 2019
• Study Start: August 5, 2020
• Primary Completion: January 15, 2026
• Study Completion: January 15, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)