Sepsis in Neonates and Antibiotic Resistance Identified by Next Generation Sequencing (the SNARINGS study)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,046
- 试验地点
- 3
- 主要终点
- The primary objective of the study is to evaluate
研究概览
简要总结
The current culture-based method for diagnosing neonatal sepsis is slow (2–5 days) and often fails to detect anaerobic, fastidious, and non-culturable pathogens, leading to diagnostic inaccuracies. To address this, the study proposes a novel Next-Generation Sequencing (NGS) approach for real-time, long-read sequencing to directly identify bacterial and fungal pathogens and antimicrobial resistance genes (ARGs) from blood samples. This method aims to enhance diagnostic speed and accuracy.
The study has three objectives: optimizing DNA extraction from small blood samples with low pathogen loads, comparing NGS-based pathogen detection with culture methods, and validating NGS accuracy using culture-positive samples. It will progress in three phases: laboratory standardization, a pilot study with culture-positive samples, and a multicentric diagnostic accuracy study in neonates with suspected sepsis.
Assuming an 18% prevalence of culture-positive sepsis (DeNIS study), a sample size of 1,046 clinically suspected cases is required to detect a sensitivity of 98% ± 2% and a specificity of 98% ± 1%, including 189 culture-positive cases. Over 2.5 years, four centers will recruit ~105 subjects annually, performing ~3,118 NGS and culture tests in total. The expected outcome is a real-time, NGS-based diagnostic method that directly detects bacterial and fungal pathogens and assesses ARGs, offering significant improvements in speed and accuracy over traditional culture-based methods for neonatal sepsis.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 0.00 Day(s) 至 28.00 Day(s)（—）
- 性别
- All
入选标准
- •Inborn or outborn neonates admitted to any of the participating neonatal units with clinical suspicion of early-onset or late-onset sepsis.
- •"Clinical suspicion of sepsis" will be defined per the NeoObs study enrollment criteria.
- •The decision to perform laboratory tests would be left to the treating team and no mandatory laboratory tests will be performed as a part of the screening process for the current study.
- •Neonates will be diagnosed with clinically suspected sepsis if at least two criteria are positive, of which at least one has to be a clinical criterion.
- •Postnatal age less than or equal to 28 days.
排除标准
- •Serious congenital malformation or
- •Critical illness or end-of-life care support that restricts sample collection for laboratory evaluation.
- •Parents of neonates who meet the above eligibility criteria will be approached for participation in the study.
- •They will be provided with a parent information sheet.
- •Neonates will be enrolled after obtaining written informed consent from a parent.
- •Information from enrolled neonates will be gathered on a case report form.
结局指标
主要结局
The primary objective of the study is to evaluate
时间窗: At presentation/baseline: Immediately upon clinical suspicion of neonatal sepsis and sample collection. | Within 12 hours of sample collection: Assessment of rapid identification of pathogens and antibiotic resistance genes using NGS. | Baseline, within 12–24 hrs
NGS Detection of Pathogens & ARGs
时间窗: At presentation/baseline: Immediately upon clinical suspicion of neonatal sepsis and sample collection. | Within 12 hours of sample collection: Assessment of rapid identification of pathogens and antibiotic resistance genes using NGS. | Baseline, within 12–24 hrs
Sensitivity, Specificity
时间窗: At presentation/baseline: Immediately upon clinical suspicion of neonatal sepsis and sample collection. | Within 12 hours of sample collection: Assessment of rapid identification of pathogens and antibiotic resistance genes using NGS. | Baseline, within 12–24 hrs
次要结局
- Identification of the spectrum of pathogens (bacterial and fungal) responsible for neonatal sepsis across participating tertiary care centers.(Detection and characterization of antimicrobial resistance genes (ARGs) associated with neonatal sepsis.)
研究者
Sourabh Dutta
Post Graduate Institute of Medical Education and Research (PGIMER) Chandigarh