Clinical trial NCT02410486: Early-Onset Sepsis an NICHD/CDC Surveillance Study
Official title: Early-Onset Sepsis an NICHD/CDC Surveillance Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infant, Newborn, Diseases
Early Onset Neonatal Sepsis
Early-Onset Meningitis
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Centers for Disease Control and Prevention
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2015-04-07
Enrollment: 570
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include all live born infants who are at least 22 weeks GA and have a birth weight \>400 grams and are delivered at NRN centers.

Brief summary: This prospective surveillance study will be conducted over a 2 year period to determine current rates of Early-Onset Sepsis (EOS)/ Early-Onset Meningitis (EOM), associated pathogens, antimicrobial resistance, signs and symptoms and infant outcomes.

Detailed description: Neonatal pathogens other than group B Streptococcus (GBS) and resistant to beta-lactam antibiotics have emerged as the most common etiologic agents of EOS and EOM among preterm and term neonates and result in high mortality rates, potentially offsetting the decreased burden of early-onset GBS disease prevented by maternal intrapartum chemoprophylaxis.

Primary Outcomes of this study:

1. To determine current hospital-based rates of early-onset neonatal infection (total, GA-specific and BW-specific, and pathogen-specific) in term and preterm infants in the era of maternal intrapartum antibiotic prophylaxis to prevent vertical transmission of group B streptococcal disease. Early-onset infection comprises EOS and/or EOM and is defined as isolation of a pathogen from blood or cerebrospinal fluid (CSF) obtained within 72 hours of birth and provision of appropriate antibiotic treatment for 5 or more days (or \<5 days if death occurs while receiving antibiotic therapy).
2. To determine the antimicrobial susceptibility patterns of organisms associated with EOS and EOM

The case control aspect of this study will address 2 major conundrums regarding EOS: Can we identify risk factors for early-onset Gram-negative infections that might lead to intervention strategies to reduce risk and can we identify infants born to mothers with clinical chorioamnionitis who are at highest risk for early-onset sepsis and thus warrant antibiotic treatment soon after birth?

Eligibility criteria: Inclusion Criteria:

* Case Surveillance: Live born infants with gestational age of at least 22 weeks and birth weight \>400 g and \<72 hours of age who are delivered at NRN hospitals and have early-onset sepsis and meningitis defined as isolation of a pathogen from blood or CSF obtained within 72 hours of birth and provision of appropriate antibiotic treatment for 5 or more days (or \<5 days if death occurs while receiving antibiotic therapy).
* Controls: Live born infants with gestational age of at least 22 weeks and birth weight \>400 g who are delivered at NRN hospitals and have not been evaluated for early-onset sepsis (\<72 hours of age) or if evaluated, they have sterile blood and/or CSF cultures and were not treated with prolonged antibiotics for clinical "culture negative" sepsis. Controls for infants with Gram-negative infection will be infants without early-onset infection. Controls for infants born to mothers with clinical chorioamnionitis will be infants without early-onset infection born to mothers with clinical chorioamnionitis. Control infants will be born at the same hospital as cases, with the same gestational age grouping as cases (22 0/7 - 28 6/7 weeks; 29 0/7 - 33 6/7 weeks; 34 0/7 - 36 6/7 weeks; and ≥ 37 weeks).

Exclusion Criteria:

* Stillbirths and infants who die in the delivery room will be excluded.
* Infants who die within 12 hours of age will be excluded if they have not been evaluated for possible infection-ie, do not have a blood culture obtained to identify EOS.

Primary outcomes:
measure: To determine current hospital-based rates of early-onset neonatal infection
timeFrame: First 72 hours
measure: To determine the antimicrobial susceptibility patterns of organisms associated with EOS and EOM
timeFrame: First 72 hours
Secondary outcomes:
measure: To identify risk factors associated with EOS/EOM due to Gram-negative pathogens (case control comparison)
timeFrame: First 72 hours
measure: To determine the clinical signs/symptoms and laboratory abnormalities associated with EOS/EOM
timeFrame: First 72 hours
measure: To identify risk factors for EOS/EOM in infants born to mothers with chorioamnionitis (case control comparison)
timeFrame: First 72 hours
measure: To determine if term infants with EOS, identified because of maternal chorioamnionitis, can be asymptomatic at birth
timeFrame: First 72 hours
measure: To determine sepsis-associated mortality rates (total, GA-specific and BW-specific, pathogen-specific) for infants with EOS/EOM
timeFrame: First 72 hours
measure: To review changes over time in overall rates of EOS and EOM, pathogens associated with infection, risk factors for infection, clinical and laboratory abnormalities, and sepsis-associated mortality
timeFrame: 9-11 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Research Institute at Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Barbara Stoll, MD
role: STUDY_DIRECTOR
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospita
name: Michele Walsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brown University, Women & Infants Hospital of Rhode Island
name: Abbot Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Michael Cotten, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Greg Sokol, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Krisa Van Meurs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Brenda Poindexter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Kristi Watterberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Myra Wyckoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Kathleen Kennedy, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Barbara Schmidt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Carl D'Angio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Institute at Nationwide Children's Hospital
name: Pablo Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Mercy Hospital Kansas City
name: William Truog, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Uday Devaskar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Bradley Yoder, MD
role: PRINCIPAL_INVESTIGATOR
References: