NICU Antibiotics and Outcomes Trial (NANO)
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|ClinicalTrials.gov Identifier: NCT03997266|
Recruitment Status : Not yet recruiting
First Posted : June 25, 2019
Last Update Posted : April 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Microbial Colonization Extreme Prematurity Early-Onset Neonatal Sepsis Late-Onset Neonatal Sepsis Necrotizing Enterocolitis of Newborn Death; Neonatal||Drug: Ampicillin Drug: Gentamycin Drug: Normal saline||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||802 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||NICU Antibiotics and Outcomes Trial|
|Estimated Study Start Date :||June 2020|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||June 2024|
Active Comparator: Empiric antibiotics
Infants will receive standard antibiotic coverage of ampicillin and gentamycin at site approved dosing guidelines while completing an evaluation for early-onset neonatal sepsis.
Placebo Comparator: Placebo
Infants will receive a volume matched placebo of normal saline while completing an evaluation for early-onset neonatal sepsis.
Drug: Normal saline
Intravenous normal saline
- 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.
- 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. ]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 [ 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 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 [ 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 is defined as death during the index hospitalization.
- Microbial diversity within infant fecal samples [ Time Frame: 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. ]Bacterial DNA will be sequenced according to established protocols. In analyses of these samples, we shall investigate three important parameters, namely, alpha diversity (Richness and Shannon Index), beta diversity, and the differential abundance of individual bacterial taxa.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997266
|Contact: Michael J Morowitz, MDfirstname.lastname@example.org|
|Contact: Alyssa M Harris, MSemail@example.com|
|United States, California|
|Sharp Mary Birch Hospital for Women & Newborns|
|San Diego, California, United States, 92123|
|Contact: Anup C Katheria, MD firstname.lastname@example.org|
|Contact: Katherine Baker Katherine.email@example.com|
|Principal Investigator: Anup C Katheria, MD|
|United States, Connecticut|
|Yale University School of Medicine|
|New Haven, Connecticut, United States, 06520-8064|
|Contact: Sarah N Taylor, MD firstname.lastname@example.org|
|Contact: Christine Henry email@example.com|
|Principal Investigator: Sarah N Taylor, MD|
|United States, Kentucky|
|University of Louisville Research Foundation Inc./Kosair Charities Pediatric Clinical Research Unit|
|Louisville, Kentucky, United States, 40202|
|Contact: Taminaruth Singh, MD firstname.lastname@example.org|
|Contact: Kristen Gossett email@example.com|
|Principal Investigator: Taminaruth Singh, MD|
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Contact: Katherine Gregory, MD firstname.lastname@example.org|
|Contact: Jennifer Filatava EFILATAVA@BWH.HARVARD.EDU|
|Principal Investigator: Katherine Gregory, MD|
|United States, Missouri|
|Kansas City, Missouri, United States, 64108|
|Contact: Vankatesh Sampath, MBBS email@example.com|
|Contact: Cheri Gauldin firstname.lastname@example.org|
|Principal Investigator: Vankatesh Sampath, MBBS|
|United States, New York|
|The Trustees of Columbia University in the City of New York|
|New York, New York, United States, 10032-3702|
|Contact: Richard A Polin, MD email@example.com|
|Contact: Caitlin Ehret firstname.lastname@example.org|
|Principal Investigator: Richard A Polin, MD|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Karen M Puopolo, MD,PhD email@example.com|
|Contact: Joan Giannetta firstname.lastname@example.org|
|Principal Investigator: Karen M Puopolo, MD,PhD|
|Alfred I. duPont for Children of the Nemours Foundation|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Zubair Aghai, MD email@example.com|
|Contact: Margaret Lafferty firstname.lastname@example.org|
|Principal Investigator: Zubair Aghai, MD|
|United States, Texas|
|University of Texas Health Science Center at San Antonio|
|San Antonio, Texas, United States, 78229|
|Contact: Joseph R Cantey, MD email@example.com|
|Contact: Robin Tragus firstname.lastname@example.org|
|Principal Investigator: Joseph R Cantey, MD|
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22903|
|Contact: David Kaufman, MD email@example.com|
|Contact: Eileen Sembrowich firstname.lastname@example.org|
|Principal Investigator: David Kaufman, MD|