NCT03997266: NANO

NICU Antibiotics and Outcomes Trial

Active, enrolled Phase 4 Last updated 23 September 2025

What this trial tests

Phase 4 trial testing Ampicillin in Microbial Colonization in 802 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

5 August 2020

Primary endpoint
1 September 2026

1 June 2027

Quick facts

Lead sponsor	Michael Morowitz
Phase	Phase 4
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	802
Start date	5 August 2020
Primary completion	1 September 2026
Estimated completion	1 June 2027
Sites	14 locations across United States

Drugs / interventions tested

• Ampicillin (AMPICILLIN) — full drug profile →
• Gentamycin — full drug profile →
• Normal saline

Conditions studied

• Microbial Colonization — all drugs for Microbial Colonization →
• Extreme Prematurity — all drugs for Extreme Prematurity →
• Early-Onset Neonatal Sepsis — all drugs for Early-Onset Neonatal Sepsis →
• Late-Onset Neonatal Sepsis — all drugs for Late-Onset Neonatal Sepsis →

Sponsor

Michael Morowitz

Who can join

Under 4 Hours, any sex, with Microbial Colonization or Extreme Prematurity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study.
   Dierikx TH, Deianova N, Groen J, Vijlbrief DC, et al · · 2022 · cited 29× · PMID 35927379 · DOI 10.1007/s00431-022-04579-5
2. The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants.
   Morowitz MJ, Katheria AC, Polin RA, Pace E, et al · · 2022 · cited 26× · PMID 35606829 · DOI 10.1186/s13063-022-06352-3
3. Advocating for the inclusion of kidney health outcomes in neonatal research: best practice recommendations by the Neonatal Kidney Collaborative.
   Reidy KJ, Guillet R, Selewski DT, Defreitas M, et al · · 2024 · cited 9× · PMID 38969825 · DOI 10.1038/s41372-024-02030-1
4. Beyond the incubator: applying a "one health" approach in the NICU.
   O'Reilly D, Livada A, Steiner L, Drew RJ, et al · · 2024 · cited 2× · PMID 39215199 · DOI 10.1038/s41390-024-03534-4
5. Necrotizing Enterocolitis: What's New and What's Next?
   Sha C, Sander WR, Bass K, Hsieh H, et al · · 2025 · cited 1× · PMID 41096926 · DOI 10.3390/ijms26199660
6. Megaplasmids associate with <i>Escherichia coli</i> and other <i>Enterobacteriaceae</i>
   Guitor AK, Wang S, Tuck OT, Firek B, et al · · 2025 · DOI 10.1101/2025.09.30.679422