Salivary Profiling in Infants Treated for Suspected Sepsis: The SPITSS Study (SPITSS)

The aim of this study is to develop a faster, safer, and more accurate method for determining if a newborn has an infection. This study involves analyzing saliva for markers of infection and inflammation known as cytokines. We will analyze infant's saliva repeatedly for inflammatory biomarkers (cytokines) within the first 36 hours of their standard of care treatment. We hypothesize that levels of these cytokines will more quickly predict which babies are truly infected and which babies are not compared to the blood tests currently being used.

Study Overview

• Status: Recruiting
• Conditions: Infection; Newborn
• Intervention / Treatment: Other: Single Molecule Array (SiMoA)

Detailed Description

Specific Aim 1: Develop a predictive model of neonatal infection based upon the expression profile of six salivary inflammatory biomarkers, CRP, procalcitonin, tumor necrosis factor-alpha (TNF-α), and interleukins (IL) 1β, 6, and 8, within the first 36 hours of treatment. Serial saliva samples collected at the initiation of antibiotic therapy and 18-36 hours into treatment from 2,250 neonatal 'rule out sepsis' evaluations will undergo multiplexed quantification of the six salivary inflammatory biomarkers. Diagnostic accuracy will be calculated and predictive models will be developed, incorporating clinical, demographic, and biomarker data.

Specific Aim 2: Validate the predictive model of neonatal infection developed in Aim 1 on an external cohort of newborns. Serial saliva samples from an additional, prospective cohort of 1,750 infants undergoing a 'rule out sepsis' evaluation will be collected to test the validity of the predictive model for neonatal infection.

Specific Aim 3: Establish normative salivary reference ranges of the inflammatory biomarkers across varying gestational ages and weights, and assess the potential of these biomarkers to predict other neonatal morbidities. Salivary samples from the subset of uninfected newborns from Aims 1 and 2 will be combined and used to establish the 95% reference intervals of the salivary inflammatory biomarkers at each time point. Salivary profiles will be correlated to discharge diagnoses (i.e. bronchopulmonary dysplasia, periventricular leukomalacia) to assess the ability of each biomarker, alone and in combination, to predict neonatal morbidities known or hypothesized to be associated with an inflammatory response.

• Study Type: Observational
• Enrollment (Anticipated): 5000

Contacts and Locations

• Study Contact: Name: Jill Maron, MD, MPH; Phone Number: 401-274-1100; Email: JMaron@Wihri.org
• Study Contact Backup: Name: Anne Kurfiss, MPH; Phone Number: 617-636-7134; Email: akurfiss@tuftsmedicalcenter.org

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Contact: James Wynn, MD; Phone Number: 352-294-5496; Email: james.wynn@peds.ufl.edu
      • Contact: Carmen Thorton, RRT; Phone Number: 352-294-8642; Email: carmenthornton@peds.ufl.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Tufts Medical Center
      • Contact: Anne Kurfiss, MPH; Phone Number: 617-636-7134; Email: akurfiss@tuftsmedicalcenter.org
      • Contact: Liz Yen, MD; Email: eyen@tuftsmedicalcenter.org
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Women and Infants' Hospital
      • Contact: Joseph Bliss, MD, Phd; Phone Number: 401-274-1122; Email: Jbliss@wihri.org
      • Contact: Steven Knapp; Email: sknapp@wihri.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Neonates < 43 weeks' gestation, currently admitted to the NICU or well-baby nursery, who undergo a rule-out sepsis evaluation and are started on antibiotics.

Description

Inclusion Criteria:

Neonates < 43 weeks' gestation, currently admitted to the NICU or well-baby nursery.

Exclusion Criteria:

Neonates suffering from a lethal genetic or chromosomal abnormality or other non-infectious, life-limiting illness, known at the time parents would be approached for consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
confirmed (culture positive) infection	at initiation-of-rule-out, at 18-to-36-hour, and change between these time points

Secondary Outcome Measures

Outcome Measure	Time Frame
confirmed (culture positive) infection or clinical infection	at initiation-of-rule-out, at 18-to-36-hour, and change between these time points

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Florida; Brigham and Women's Hospital; Women and Infants Hospital of Rhode Island

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2019
• Primary Completion (Anticipated): May 31, 2024
• Study Completion (Anticipated): May 31, 2024

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 5, 2022
• Last Update Submitted That Met QC Criteria: August 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis
• Other Study ID Numbers: 13372

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The de-identified data set will be submitted to NIH.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No