Microbial ColonizationPhase 4NANONCT03997266
NICU Antibiotics and Outcomes Trial
A Phase 4 study testing Ampicillin, Gentamycin and Normal saline in people with Microbial Colonization and Extreme Prematurity, run by Michael Morowitz at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 4 hours
- Conditions the study is for
- Microbial Colonization, Extreme Prematurity, Early-Onset Neonatal Sepsis
- What is being tested?
- Ampicillin, Gentamycin and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 359 participants
- Where
- 14 sitesUnited States
- Study dates
- 5 Aug 2020to 15 Jan 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 4 hours
- All sexes
- No healthy volunteers
- Child
- Inclusion criteria: We will enroll newborn infants with gestational age of 23-30 weeks 6 days infants at participating study sites will be eligible.
II. Exclusion criteria:
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Penn State Medical College
Hershey, Pennsylvania, 17033
University of Louisville Research Foundation Inc./Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, 40202
USA Children's and Women's Hospital
Mobile, Alabama, 36688
Yale University School of Medicine
New Haven, Connecticut, 06520-8064
The Trustees of Columbia University in the City of New York
New York, New York, 10032-3702
Pennsylvania Hospital/The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Alfred I. duPont for Children of the Nemours Foundation
Philadelphia, Pennsylvania, 19107
Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
Golisano Children's Hospital at University of Rochester
Rochester, New York, 14642
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
University of South Flordia Health
Tampa, Florida, 33606
Maria Fareri Children's Hospital at Westchester Medical Center
Valhalla, New York, 10595
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
About this study
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.
Read the detailed description
Randomization and blinding. Physicians will screen infants based on inclusion/exclusion criteria. The site coordinator will confirm eligibility with the treating physician and input patient data into the web based system. Once data is inputted, the coordinator will randomize eligible families 1:1 using web-based block randomization stratified by study site to receive EA or placebo. Multiples (i.e. siblings) will be randomized to the same treatment arm. Randomization will be sent to the investigational pharmacy via email, where study drug will be drawn. Participants, treating clinicians, and study staff will all be blinded to allocation. Outcome assessors and statistical summaries for trial monitoring will be unaware of group allocation. Unblinded data evaluation during the trial will be restricted to a designated study statistician and the Data and Safety Monitoring Board (DSMB). Investigators will be unblinded and analyses initiated only after all data collection forms are completed, data queries resolved, and data are locked for analysis.
Intervention. Following randomization, the coordinator will contact the attending physician, nurse practitioner and/or other providers as appropriate, and nurse to inform them that randomization has been completed. The intervention consists of administering either conventional EA or placebo while completing an evaluation for early onset sepsis. Timing of drug administration will be closely monitored. Enrolled subjects will receive EITHER ampicillin and gentamicin at site approved dosing guidelines OR volume matched equivalent of normal saline. These dosing regimens are derived from updated published guidelines for neonates. No masking is required as each of these solutions is clear.
The study drug will be ordered and in many cases discontinued just as EA would normally be ordered and discontinued; specifically, this means that the drugs will be ordered and administered within 4 hours of life and then discontinued at the discretion of the attending neonatologist. Typically this occurs when blood culture results are deemed negative (expected in > 95% of study subjects). The study protocol will allow the first dose of study drug to be administered as late as 4 hours after delivery. Research coordinators will follow daily orders on all study subjects.
Fecal sample collection. Samples will be obtained exclusively for research purposes, and there will be no testing of patients beyond obtaining microbiome samples, and recording demographic data and clinical history. Spontaneously expelled fecal samples for microbiome analyses will be obtained weekly from study subjects through the first 8 weeks of life, and monthly thereafter until death or discharge.
Infant blood draw. An additional research blood sample for genetic analysis will be drawn one time and should be done at the time of clinical blood draws. However, if this blood draw is missed, it can be done in the neonate's first week of life. A volume of 0.3 to 0.4mL will be drawn in EDTA tubes and shaken well. After the sample is collected, it will be frozen for shipment. The blood draw will be performed by NICU personnel who routinely draw blood on preterm babies. It will be either the bedside nurse or the respiratory therapist depending on whether the blood is drawn from an umbilical catheter or by heelstick.
Maternal vaginal swab and rectal swabs at delivery will be collected. If a rectal swab was not collected at the time of delivery, a maternal fecal sample during the first week postpartum will be collected in its place. Samples will be cryopreserved at -80C.
An electronic database will be used to track sample collection and storage history.
- Conditions
- Microbial Colonization, Extreme Prematurity, Early-Onset Neonatal Sepsis, Late-Onset Neonatal Sepsis, Necrotizing Enterocolitis of Newborn, Death; Neonatal
- Being tested
- Ampicillin, Gentamycin, Normal saline
- Keywords
- premature birth, human microbiome, antibiotics
- Medical subject headings
- Communicable Diseases, Neonatal Sepsis, Perinatal Death, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmpicillinDrug
Intravenous ampicillin
GentamycinDrug
Intravenous gentamycin
Normal salineDrug
Intravenous normal saline
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Death is defined as death during the index hospitalization.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2019
- Study start5 Aug 2020
- Primary completion15 Jan 2026
- Study completion15 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Microbial ColonizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 359 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Morowitz
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Michael Morowitz, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03997266
- Sponsor's protocol ID
- STUDY20110298
- Other IDs
- R01HD097578
- Acronym
- NANO
- Status last verified
- Apr 2026
- First submitted
- 2 Jun 2019
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35606829
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NICU Antibiotics and Outcomes Trial
- ClinicalTrials.gov ID
- NCT03997266
- Acronym / sponsor ID
- NANO / STUDY20110298
- Conditions
- Microbial Colonization, Extreme Prematurity, Early-Onset Neonatal Sepsis, Late-Onset Neonatal Sepsis, Necrotizing Enterocolitis of Newborn, Death; Neonatal
- Keywords
- premature birth, human microbiome, antibiotics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 359 participants (actual)
- Lead sponsor
- Michael MorowitzUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 5 Aug 2020 (actual)
- Primary completion
- 15 Jan 2026 (actual)
- Study completion
- 15 Jan 2026 (actual)
- First posted
- 25 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Randomization and blinding. Physicians will screen infants based on inclusion/exclusion criteria. The site coordinator will confirm eligibility with the treating physician and input patient data into the web based system. Once data is inputted, the coordinator will randomize eligible families 1:1 using web-based block randomization stratified by study site to receive EA or placebo. Multiples (i.e. siblings) will be randomized to the same treatment arm. Randomization will be sent to the investigational pharmacy via email, where study drug will be drawn. Participants, treating clinicians, and study staff will all be blinded to allocation. Outcome assessors and statistical summaries for trial monitoring will be unaware of group allocation. Unblinded data evaluation during the trial will be restricted to a designated study statistician and the Data and Safety Monitoring Board (DSMB). Investigators will be unblinded and analyses initiated only after all data collection forms are completed, data queries resolved, and data are locked for analysis.
Intervention. Following randomization, the coordinator will contact the attending physician, nurse practitioner and/or other providers as appropriate, and nurse to inform them that randomization has been completed. The intervention consists of administering either conventional EA or placebo while completing an evaluation for early onset sepsis. Timing of drug administration will be closely monitored. Enrolled subjects will receive EITHER ampicillin and gentamicin at site approved dosing guidelines OR volume matched equivalent of normal saline. These dosing regimens are derived from updated published guidelines for neonates. No masking is required as each of these solutions is clear.
The study drug will be ordered and in many cases discontinued just as EA would normally be ordered and discontinued; specifically, this means that the drugs will be ordered and administered within 4 hours of life and then discontinued at the discretion of the attending neonatologist. Typically this occurs when blood culture results are deemed negative (expected in > 95% of study subjects). The study protocol will allow the first dose of study drug to be administered as late as 4 hours after delivery. Research coordinators will follow daily orders on all study subjects.
Fecal sample collection. Samples will be obtained exclusively for research purposes, and there will be no testing of patients beyond obtaining microbiome samples, and recording demographic data and clinical history. Spontaneously expelled fecal samples for microbiome analyses will be obtained weekly from study subjects through the first 8 weeks of life, and monthly thereafter until death or discharge.
Infant blood draw. An additional research blood sample for genetic analysis will be drawn one time and should be done at the time of clinical blood draws. However, if this blood draw is missed, it can be done in the neonate's first week of life. A volume of 0.3 to 0.4mL will be drawn in EDTA tubes and shaken well. After the sample is collected, it will be frozen for shipment. The blood draw will be performed by NICU personnel who routinely draw blood on preterm babies. It will be either the bedside nurse or the respiratory therapist depending on whether the blood is drawn from an umbilical catheter or by heelstick.
Maternal vaginal swab and rectal swabs at delivery will be collected. If a rectal swab was not collected at the time of delivery, a maternal fecal sample during the first week postpartum will be collected in its place. Samples will be cryopreserved at -80C.
An electronic database will be used to track sample collection and storage history.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empiric antibiotics | Active comparator | Drug: Ampicillin, Drug: GentamycinInfants will receive standard antibiotic coverage of ampicillin and gentamycin at site approved dosing guidelines while completing an evaluation for early-onset neonatal sepsis. |
| Placebo | Placebo comparator | Drug: Normal salineInfants will receive a volume matched placebo of normal saline while completing an evaluation for early-onset neonatal sepsis. |
Who may qualify
- Ages
- Up to 4 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmpicillinIntravenous ampicillin | Drug | Empiric antibiotics |
| GentamycinIntravenous gentamycin | Drug | Empiric antibiotics |
| Normal salineIntravenous normal saline | Drug | Placebo |
Primary outcome
Composite incidence of NEC, LOS, or death
Time frame: 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.
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.
3 secondary outcomes
NEC
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Derived from this study: PubMed 35606829Morowitz 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ampicillin, Gentamycin and Normal saline in people with Microbial Colonization and Extreme Prematurity, run by Michael Morowitz at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite incidence of NEC, LOS, or death (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03997266, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.