NANO-FU: NICU Antibiotics and Outcomes (NANO) Follow-up Study

• Sponsor: Sharp HealthCare (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05977400
• Collaborator: University of Pittsburgh (Other), Morgan Stanley Children's Hospital (Other), University of Louisville (Other), Sharp Mary Birch Hospital for Women & Newborns (Other), Children's Hospital of Philadelphia (Other), Jefferson Medical College of Thomas Jefferson University (Other), University of South Florida (Other), Westchester Medical Center (Other), Yale University (Other), The University of Texas Health Science Center at San Antonio (Other), Penn State University (Other), State University of New York - Downstate Medical Center (Other), Mount Sinai Hospital, Canada (Other)
• Enrollment: 802
• Locations: 15
• Arms: 2
• Anticipated Duration (Months): 59
• Patients Per Site: 53.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Premature Birth; Antibiotics; Neurodevelopment	Drug: Ampicillin; Drug: Gentamicin; Drug: Placebo	Phase 3

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

• Study Type: Interventional
• Anticipated Enrollment: 802 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: NICU Antibiotics and Outcomes Follow-Up Study
• Anticipated Study Start Date: Apr 1, 2024
• Anticipated Primary Completion Date: Mar 1, 2029
• Anticipated Study Completion Date: Mar 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Very preterm infants that receive empiric antibiotic treatment in the first 48 hours of life 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; Intravenous Ampicillin; Drug: Gentamicin; Intravenous Gentamicin
Placebo Comparator: Very preterm infants that do not receive empiric antibiotic treatment in the first 48 hours of life 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; Intravenous Normal Saline

Outcome Measures

Primary Outcome Measures

1. Rate of neurodevelopmental impairment or Death [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.

2. DOOR probability Distribution [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 23 Weeks to 30 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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:

1. 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

2. 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

3. 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

4. Infants with ongoing hemodynamic instability requiring vasopressors or more than one fluid bolus at time of randomization

5. Clinician concern for sepsis due to physical exam findings or clinical history of mother or infant

6. Major congenital anomalies

7. Infants not anticipated to survive beyond 72 hours

8. Infants who have received antibiotics prior to randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sharp Mary Birch Hospital for Women & Newborns	San Diego	California	United States	92123
2	Yale University	New Haven	Connecticut	United States	06511
3	University of South Florida	Tampa	Florida	United States	33620
4	University of Louisville	Louisville	Kentucky	United States	40292
5	State University of New York Downstate	Brooklyn	New York	United States	11203
6	Columbia University	New York	New York	United States	10027
7	University of Rochester	Rochester	New York	United States	14611
8	Westchester Medical Center	Valhalla	New York	United States	10595
9	The Pennsylvania State University	Hershey	Pennsylvania	United States	17033-0850
10	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	Jefferson Medical College of Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
12	Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
13	The University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
14	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
15	Sinai Health System	Toronto		Canada

Sponsors and Collaborators

• Sharp HealthCare
• 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

Investigators

• Principal Investigator: Anup Katheria, MD, Sharp HealthCare

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anup Katheria, M.D., PI, Sharp HealthCare
• ClinicalTrials.gov Identifier: NCT05977400
• Other Study ID Numbers: NANO Follow-Up
• First Posted: Aug 4, 2023
• Last Update Posted: Aug 4, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Premature Birth; Gentamicins; Ampicillin

Study Results

No Results Posted as of Aug 4, 2023