Biomarker Discovery, Newborn Sepsis, Sepsis
Conditions
Keywords
t6a, newborn sepsis, infectious disease biomarker, biomarker
Brief summary
This bi-center study aims to assess the efficacy of a new biomarker, N6-threonylcarbamoyladenosine (t6A), for the early diagnosis of Early-Onset Sepsis (EOS) in newborns.
Detailed description
This bi-center study aims to assess the efficacy of a new biomarker, N6-threonylcarbamoyladenosine (t6A), for the early diagnosis of Early-Onset Sepsis (EOS) in newborns. Background: EOS is a significant concern for newborns, especially preterm infants, with a high mortality rate. Current diagnostic methods, like blood cultures, have limitations due to non-specific clinical presentations and slow turnaround times. Existing biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and Interleukin-6 (IL-6) also have limitations in terms of early detection and specificity. Objective: To facilitate the early diagnosis of EOS in newborns at risk for bacterial infection on day one. Hypotheses: t6A levels will rapidly increase in newborns with suspected EOS, allowing for early and precise identification from non-EOS neonates. Circulating t6A will demonstrate higher diagnostic accuracy (positive and negative predictive values) compared to existing biomarkers like PCT, CRP, and IL-6. Methodology: This will be an open-label prospective cohort bi-center study conducted at the Private Medical University of Salzburg, Austria together with the Medical University of Wrocław in cooperation with the Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Vienna Austria Study Population: Newborn infants requiring blood testing for suspected bacterial infection or routine screening who meet specific inclusion criteria and whose caregivers provide informed consent. Exclusion criteria include refusal to participate or current antibiotic treatment. Control Group: 50 healthy newborn infants undergoing routine blood testing for other reasons (e.g., thyroid hormone testing). Data Collection: Blood samples (20 µl using Neoteryx® Microsampling kit) will be collected via heel prick during routine patient care within the first 24 hours of life. Clinical and blood value data will also be collected. Samples will be analyzed for t6A, CBC, CRP, PCT, and IL-6. Sepsis Confirmation: Bacterial infection will be confirmed using adapted NEO-KISS criteria, which include clinical sepsis and microbiologically confirmed sepsis (with and without coagulase-negative staphylococci). Timeline: Patient enrollment will occur between February 1, 2026, and January 31, 2029. Sample Size: A minimum of 210 participants (105 sepsis, 105 control) is planned to achieve adequate statistical power, based on AUC values of t6A and PCT from a previous study. Data Management: Patient data will be anonymized with three-digit identification numbers. Blood samples will be sent to Pharm-analyt for testing. Analysis/Statistics: Data will be analyzed using R. Primary outcome (differences in t6A levels) will be assessed using t-tests or Wilcoxon tests. Secondary outcomes (comparison of AUCs for t6A vs. IL-6 and CRP) will use DeLong's test with Bonferroni-Holms correction.
Interventions
None listed
Sponsors
Salzburger Landeskliniken
Wroclaw Medical University
Ludwig Boltzmann Institute for Traumatology - The research center in cooperation with AUVA
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Newborn infants who require blood testing for screening for bacterial infection OR treating physician suspects bacterial infection in newborn infant * Signed informed consent form
Exclusion criteria
1. Refusal to participate in study or not providing written informed consent by caregivers/parents 2. Antibiotic treatment of any kind.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Clinical Sepsis | 12 Hours | 1\. Clinical Sepsis (no pathogen detected): All of: * Initiation of adequate antimicrobial therapy ≥5 days by attending physician * No pathogen detected in blood culture or not tested * No clear infection elsewhere AND at least 2 of: * Fever (\>38°C) or temperature instability or hypothermia (\<36.5°C) * Tachycardia (\>200/min) or new/increased bradycardia (\<80/min) * Capillary refill \>2s * New/increased apnoea (\>20 s) * Unexplained metabolic acidosis (BE \< -10 mval/l) * New onset hyperglycaemia (\>140 mg/dl) * Other sepsis signs (skin color, abnormal labs, increased oxygen demand, unstable status, apathy) |
| Number of participants with Microbiologically Confirmed Sepsis (excluding coagulase negative staphylococci CNS) | 12 Hours | Microbiologically Confirmed Sepsis (excluding coagulase negative staphylococci CNS) AND at least 2 of: * Fever (\>38°C) or temperature instability or hypothermia (\<36.5°C) * Tachycardia (\>200/min) or new/increased bradycardia (\<80/min) * Capillary refill \>2s * New/increased apnoea (\>20 s) * Unexplained metabolic acidosis (BE \< -10 mval/l) * New onset hyperglycaemia (\>140 mg/dl) * Other sepsis signs (skin color, abnormal labs, increased oxygen demand, unstable status, apathy) |
| Number of participants with Microbiologically confirmed Sepsis with CNS | 12 Hours | Microbiologically confirmed sepsis with CNS as the sole pathogen One lab value (without other plausible cause) * CRP \>2mg/dl * I/T ratio \> 0.2 * Platelets \<100/nl * Leukocytes \<5/nl AND at least 2 of: * Fever (\>38°C) or temperature instability or hypothermia (\<36.5°C) * Tachycardia (\>200/min) or new/increased bradycardia (\<80/min) * Capillary refill \>2s * New/increased apnoea (\>20 s) * Unexplained metabolic acidosis (BE \< -10 mval/l) * New onset hyperglycaemia (\>140 mg/dl) * Other sepsis signs (skin color, abnormal labs, increased oxygen demand, unstable status, apathy) |
Countries
Austria, Poland
Contacts
CONTACTLorenz Stana-Hackenberg, MD
Outcome results
None listed