NICU Antibiotics and Outcomes Trial (NANO)
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| ClinicalTrials.gov Identifier: NCT03997266 |
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Recruitment Status :
Recruiting
First Posted : June 25, 2019
Last Update Posted : February 16, 2023
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| 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 |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | NICU Antibiotics and Outcomes Trial |
| Actual Study Start Date : | August 5, 2020 |
| Estimated Primary Completion Date : | September 1, 2025 |
| Estimated Study Completion Date : | June 1, 2026 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Ampicillin
Intravenous ampicillin Drug: Gentamycin Intravenous gentamycin |
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Placebo Comparator: Placebo
Infants will receive a volume matched placebo of normal saline while completing an evaluation for early-onset neonatal sepsis.
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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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | up to 4 Hours (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
I. 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
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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
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, MD | 412-692-5976 | michael.morowitz@chp.edu | |
| Contact: Kathryn C Little, RN | 412-841-2745 | littlekc@upmc.edu |
| United States, California | |
| Sharp Mary Birch Hospital for Women & Newborns | Recruiting |
| San Diego, California, United States, 92123 | |
| Contact: Anup C Katheria, MD anup.katheria@sharp.com | |
| Contact: Catherine Salcido, RN catherine.salcido@sharp.com | |
| Principal Investigator: Anup C Katheria, MD | |
| United States, Connecticut | |
| Yale University School of Medicine | Recruiting |
| New Haven, Connecticut, United States, 06520-8064 | |
| Contact: Matthew Bizzarro, MD matthew.bizzarro@yale.edu | |
| Contact: Christine Henry christine.henry@yale.edu | |
| Principal Investigator: Matthew Bizzarro, MD | |
| United States, Florida | |
| University of South Flordia Health | Recruiting |
| Tampa, Florida, United States, 33606 | |
| Contact: Tara Randis trandis@usf.edu | |
| Contact: Marcia Kneusel, RNC 813-844-3395 mkneusel@usf.edu | |
| United States, Kansas | |
| University of Kansas Medical Center | Recruiting |
| Kansas City, Kansas, United States, 66160 | |
| Contact: Michael Nyp, MD mfnyp@cmh.edu | |
| Contact: Miah Ruffin 816-315-1725 mruffin@cmh.edu | |
| United States, Kentucky | |
| University of Louisville Research Foundation Inc./Kosair Charities Pediatric Clinical Research Unit | Recruiting |
| Louisville, Kentucky, United States, 40202 | |
| Contact: Taminaruth Singh, MD tamina.singh@louisville.edu | |
| Contact: Jennifer Hay jenn.hay@louisville.edu | |
| Principal Investigator: Taminaruth Singh, MD | |
| United States, Missouri | |
| Children's Mercy | Recruiting |
| Kansas City, Missouri, United States, 64108 | |
| Contact: Howard Kilbride, MD hkilbride@cmd.edu | |
| Contact: Cheri Gauldin cagauldin@cmh.edu | |
| Principal Investigator: Howard Kilbride, MD | |
| United States, New York | |
| The Trustees of Columbia University in the City of New York | Recruiting |
| New York, New York, United States, 10032-3702 | |
| Contact: Richard A Polin, MD rap32@cumc.columbia.edu | |
| Contact: Caitlin Ehret ce2310@cumc.columbia.edu | |
| Principal Investigator: Richard A Polin, MD | |
| Maria Fareri Children's Hospital at Westchester Medical Center | Recruiting |
| Valhalla, New York, United States, 10595 | |
| Contact: LaGamma Edmund, MD edmund_lagamma@nymc.edu | |
| Contact: Clare Giblin, RN 914-493-1442 clare.giblin@wmchealth.org | |
| United States, Pennsylvania | |
| Penn State Medical College | Recruiting |
| Hershey, Pennsylvania, United States, 17033 | |
| Contact: Chintan Gandhi, MD 717-531-5656 cgandhi@pennstatehealth.psu.edu | |
| Contact: Chelsea Winters 717-531-5656 cwinters2@pennstatehealth.psu.edu | |
| Pennsylvania Hospital/The Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact: Karen M Puopolo, MD,PhD karen.puopolo@pennmedicine.upenn.edu | |
| Contact: Toni Mancini toni.mancini@pennmedicine.upenn.edu | |
| Principal Investigator: Karen M Puopolo, MD,PhD | |
| Alfred I. duPont for Children of the Nemours Foundation | Recruiting |
| Philadelphia, Pennsylvania, United States, 19107 | |
| Contact: Zubair Aghai, MD zubair.aghai@nemours.org | |
| Contact: Margaret Lafferty margaret.lafferty@nemours.org | |
| Principal Investigator: Zubair Aghai, MD | |
| Magee Womens Hospital | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| Contact: Michael J Morowitz, MD 412-692-5986 michael.morowitz@chp.edu | |
| Contact: Kathryn C Little, RN 412-841-2745 littlekc@upmc.edu | |
| Principal Investigator: Michael J Morowitz, MD | |
| Sub-Investigator: Toby Yanowitz, MD | |
| United States, Texas | |
| University of Texas Health Science Center at San Antonio | Recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Joseph R Cantey, MD cantey@uthscsa.edu | |
| Contact: Dianna Anzueto anzuetod@uthscsa.edu | |
| Principal Investigator: Joseph R Cantey, MD | |
| Responsible Party: | Michael Morowitz, Associate Professor, University of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT03997266 |
| Other Study ID Numbers: |
PRO18010284 1R01HD097578-01 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 25, 2019 Key Record Dates |
| Last Update Posted: | February 16, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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premature birth human microbiome antibiotics |
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Neonatal Sepsis Infant, Newborn, Diseases Anti-Bacterial Agents Sepsis Toxemia Communicable Diseases Infections Enterocolitis Enterocolitis, Necrotizing Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes |
Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Intestinal Diseases Disease Attributes Gentamicins Ampicillin Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |