NICU Antibiotics and Outcomes Trial (NANO)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03997266|
Recruitment Status : Not yet recruiting
First Posted : June 25, 2019
Last Update Posted : June 25, 2019
|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 3|
Randomization and blinding. For each infant born to a mother that has provided consent, a coordinator will assess eligibility. Thus, there will be a two-part screening to first determine maternal eligibility, and then to determine infant eligibility. Investigative pharmacists 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. 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 (75 mg/kg/dose every 8 hours) and gentamicin (5 mg/kg/dose every 48 hours) 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. A maternal vaginal swab at delivery and a maternal fecal sample during the first week postpartum will also be collected. 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 :||November 2019|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||June 2024|
Active Comparator: Empiric antibiotics
Infants will receive standard antibiotic coverage of ampicillin (75 mg/kg/dose every 8 hours) and gentamycin (5 mg/kg/dose given every 48 hours) 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 or 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.
- Total antibiotic days [ Time Frame: From the time and day or 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. ]total number of calendar days that the subject received any intravenous or oral antibiotics
- Days to full enteral feedings [ Time Frame: From the time and day or 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. ]receiving a total volume of enteral nutrition that will support the infant's metabolism and growth without supplemental parental nutrition.
- Weight z-scores [ Time Frame: Weight z-scores will be calculated weekly after randomization through discharge from the subjetcs birth hospital up until 50 weeks. ]A z-score is a standard score that can placed on a normal distribution curve. The z-score is obtained using the baby's weight and gestational age
- Length z-scores [ Time Frame: Length z-scores will be calculted weekly from randomization through discharge from the subject's birth hospital up until 50 weeks ]An Infant length z-score is based on a measurement with the infant in the in the recumbent position using a calibrated length board. Length will be recorded in centimeters.
- Head circumference [ Time Frame: Head circumference will be assessed and recorded weekly from randomization through discharge from the subject's birth hospital up until 50 weeks ]Head circumference or OFC is measured over the most prominent part on the back of the infants' head (occiput) and just above the eyebrows (supraorbital ridges). This will be done using a flexible, non-stretchable tape measure and will be recorded in centimeters.
- Retinopathy of prematurity (ROP) [ Time Frame: ROP will be assessed from randomization throught the subject's death or discharge from the birth hospital through 50 weeks. ]ROP is the interruption of the normal progression of retinal vascularization or retinal detachment in premature infants. ROP is diagnosed by direct examination performed by a neonatal ophthalmologist as clinically indicated.
- Bronchopulmonary dysplasia [ Time Frame: From 36 weeks post menstrual age until death or discharge from the birth hospital up until 50 weeks. ]Bronchopulmonary dysplasia (BPD) is a chronic lung disease defined by the Vermont Oxford Network (VON) definition as an FiO2 requirement at 36 weeks post menstrual age.
- Intraventricular hemorrhage (IVH) [ Time Frame: From randomization until day of life 28 up until 5 weeks. ]Subependymal, intraventricular, or intraparenchymal hemorrhage on cranial US, MRI, or CT.
- Periventricular leukomalacia [ Time Frame: From randomization throught the subject's death or discharge from the birth hospital up until 50 weeks. ]Cystic periventricular leukomalacia on cranial US, MRI, or CT.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997266
|Contact: Michael J Morowitz, MDemail@example.com|
|Contact: Robyn W Baker, BSNfirstname.lastname@example.org|