Premature BirthPhase 3NANO-FUNCT05977400
NICU Antibiotics and Outcomes (NANO) Follow-up Study
A Phase 3 study testing Ampicillin and Gentamicin in people with Premature Birth and Antibiotics, run by Sharp HealthCare at 15 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 23 to 30 weeks
- Conditions the study is for
- Premature Birth, Antibiotics, Neurodevelopment
- What is being tested?
- Ampicillin and Gentamicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 802 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Apr 2024to Mar 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 23 to 30 weeks
- All sexes
- No healthy volunteers
- Child
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:
- 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:
- 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.
Trial locations and contacts
15 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Rebecca Dorner, MD contact
15 sites in 2 countries
United States14 sites
State University of New York Downstate
Brooklyn, New York, 11203
Jacob Aranda, MD, jacob.aranda@downstate.edu
The Pennsylvania State University
Hershey, Pennsylvania, 17033-0850
Chintan Gandhi, MD, cgandhi@pennstatehealth.psu.edu
University of Louisville
Louisville, Kentucky, 40292
Elizabeth Schumacher, eschumacher@louisville.edu
Tamina Singh, MD, tamina.singh@louisville.edu
Yale University
New Haven, Connecticut, 06511
Angela Montgomery, MD, angela.montgomery@yale.edu
Columbia University
New York, New York, 10027
Rich Polin, rap32@cumc.columbia.edu
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Karen Puopolo, MD, Karen.Puopolo@pennmedicine.upenn.edu
Jefferson Medical College of Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15213
The University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Michael Morowitz, MD, michael.morowitz@chp.edu
University of Rochester
Rochester, New York, 14611
Carl D'Angio, MD, Carl_Dangio@URMC.Rochester.edu
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Leslie-Anne Dietrich, dietrichL3@uthscsa.edu
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
Anup C Katheria, MD, 858-939-4170, anup.katheria@sharp.com
Felix T Ines, RCP-RRT, 858-939-4136, felix.ines@sharp.com
University of South Florida
Tampa, Florida, 33620
Tara Randis, MD, trandis@usf.edu
Westchester Medical Center
Valhalla, New York, 10595
Canada1 site
Sinai Health System
Toronto
Ashraf Kharrat, MD, Ashraf.Kharrat@sinaihealth.ca
About this study
Official title: NICU Antibiotics and Outcomes Follow-Up Study
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.
Read the detailed 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.
- Conditions
- Premature Birth, Antibiotics, Neurodevelopment
- Being tested
- Ampicillin, Gentamicin, Placebo
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmpicillinDrug
Intravenous Ampicillin
GentamicinDrug
Intravenous Gentamicin
PlaceboDrug
Intravenous Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 months corrected gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2023
- Study startApr 2024 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature BirthStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 802 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sharp HealthCare
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh, Morgan Stanley Children's Hospital, University of Louisville, Sharp Mary Birch Hospital for Women & Newborns, Children's Hospital of Philadelphia, Jefferson Medical College of Thomas Jefferson University, University of South Florida, Westchester Medical Center, Yale University, The University of Texas Health Science Center at San Antonio, Penn State University, State University of New York - Downstate Medical Center, Mount Sinai Hospital, Canada
- Responsible party
- Principal investigator, Anup Katheria, M.D., Sharp HealthCare
- Investigators
- Anup Katheria, MD, Principal investigator, Sharp HealthCare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05977400
- Sponsor's protocol ID
- NANO Follow-Up
- Acronym
- NANO-FU
- Status last verified
- Jul 2023
- First submitted
- 24 May 2021
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NICU Antibiotics and Outcomes Follow-Up Study
- ClinicalTrials.gov ID
- NCT05977400
- Acronym / sponsor ID
- NANO-FU / NANO Follow-Up
- Conditions
- Premature Birth, Antibiotics, Neurodevelopment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 802 participants (estimated)
- Lead sponsor
- Sharp HealthCareUniversity, hospital or other
- Collaborators
- University of Pittsburgh, Morgan Stanley Children's Hospital, University of Louisville, Sharp Mary Birch Hospital for Women & Newborns, Children's Hospital of Philadelphia, Jefferson Medical College of Thomas Jefferson University, University of South Florida, Westchester Medical Center, Yale University, The University of Texas Health Science Center at San Antonio, Penn State University, State University of New York - Downstate Medical Center, Mount Sinai Hospital, Canada
- Study start
- Apr 2024 (estimated)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 4 Aug 2023 (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 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.
Detailed 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.
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 |
|---|---|---|
| Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life | Active comparator | Drug: Ampicillin, Drug: GentamicinNeonates in this group will have been enrolled and randomized into the NANO trial and received a blinded 48 hour course of empiric antibiotic treatment. |
| Very preterm infants that do not receive empiric antibiotic treatment in the first 48 hours of life | Placebo comparator | Drug: PlaceboNeonates in this group will have been enrolled and randomized into the NANO trial and received a blinded 48 hour course of placebo. |
Who may qualify
- Ages
- 23 to 30 weeks
- 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 | Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life |
| GentamicinIntravenous Gentamicin | Drug | Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life |
| PlaceboIntravenous Normal Saline | Drug | Very preterm infants that do not receive empiric antibiotic treatment in the first 48 hours of life |
Primary outcome
Rate of neurodevelopmental impairment or Death
Time frame: 24 months corrected gestational age
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.
DOOR probability Distribution
Time frame: 24 months corrected gestational age
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Individual participant dataSharing planned: Yes. Data will be made available per NICHD requirements (National Institute of Child Health and Human Development).
Related trials for Premature Birth
Not yet recruiting
nCPAP-NAVA-Backup Versus Standard nCPAP for Severe Apnea in Preterm Infants ≤28 Weeks
Apnea of Prematurity
Recruiting
Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Preterm Birth, Enterocolitis, Necrotizing
RecruitingObservational study
Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study
NEC - Necrotizing Enterocolitis
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
RecruitingObservational study
Growing Little PEAPODS Study
Premature Birth, Premature Infant
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.
Rebecca Dorner, MD contact
Anup Katheria, MD principal investigator
Sharp HealthCare
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ampicillin and Gentamicin in people with Premature Birth and Antibiotics, run by Sharp HealthCare at 15 sites in 2 countries.
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: opening soon, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anup Katheria, MD (8589394170, anup.katheria@sharp.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of neurodevelopmental impairment or Death (time frame: 24 months corrected gestational age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Aug 2023.