Clinical Value of Metagenomic Sequencing in Neonatal Sepsis

Assessing the Clinical Value of Metagenomics Sequencing for the Diagnosis and Treatment of Neonatal Sepsis: a Multicenter Prospective Observational Study

This study aimed to enroll 2000 neonatal patients with suspected sepsis or clinical diagnosed sepsis. These patients will undergo both conventional methods and metagenomics sequencing to detect the pathogenic microorganisms of sepsis. The purpose of this study was to assess the clinical value of metagenomics sequencing for the diagnosis and treatment of neonatal sepsis.

Study Overview

• Status: Completed
• Conditions: Neonatal Sepsis

Detailed Description

Infectious diseases remain leading causes of mortality and morbidity in children. Rapid and accurate diagnosis of infectious diseases in children is important for developing an effective treatment and management strategy. However, the current diagnosis of infectious agents mainly depends on culture and molecular testing. Both of the methods either has long turnaround times or narrow detection range. Metagenome next generation sequencing (mNGS) has been applied to the diagnosis of central nervous system infection, lower respiratory tract infection and sepsis, which showed high positive rate, short turnaround time. As a multi-center prospective observational clinical study, the study intends to enroll 2000 suspected neonatal sepsis cases from multiple centers. Culture, classical PCR and mNGS were performed simultaneously. This study is one of the few multi-center studies in China to evaluate the value of mNGS in the diagnosis and treatment of neonatal sepsis, and will provide representative data for the distribution characteristics of pathogen spectrum of children in the real world and the clinical diagnosis and treatment value of mNGS.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201102
    • Children Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 4 weeks (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study focuses on neonates with primary clinical diagnosis of sepsis.

Description

Inclusion Criteria:

• Neonates with suspected early-onset sepsis or late-onset sepsis;
• Neonates diagnosed with clinical sepsis.

Exclusion Criteria:

• Died before the results of conventional methods test or metagenomics test were obtained;
• Suffering from diseases of the blood system;
• Suffering from malignant tumor;
• Birth defects, congenital heart disease or autoimmune disease.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of metagenomics sequencing	The diagnostic performance of metagenomics sequencing for neonatal sepsis was evaluated by calculating sensitivity and specificity. Sensitivity = mNGS positive samples/ reference standard methods positive samples; Specificity = mNGS negative samples/ reference standard methods negative samples.	From the date of first samples enrolled until the last samples detected, up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical impact of metagenomics sequencing	Clinical impact of metagenomics sequencing was evaluated by calculating the positive impact rate, negative impact rate and no impact rate. Positive impact rate = positive impact cases/ total cases; negative impact rate = negative impact cases/ total cases; no impact rate = no impact cases/ total cases. Clinical impact was assessed according to predefined objective grading criteria.	From the date of first samples enrolled until the last samples detected, up to 2 years.

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: Shengjing Hospital; The First Hospital of Jilin University; Henan Provincial People's Hospital; Xiamen Children's Hospital; Kunming Children's Hospital; Nanjing Maternity and Child Health Care Hospital; Hunan Children's Hospital; Tianjin Central Hospital of Gynecology Obstetrics; Children's Hospital of Nanjing Medical University; Wuhan Children's Hospital; Jiangxi Maternal and Child Health Hospital; Northwest Women's and Children's Hospital, Xi'an, Shaanxi; Jiangxi Children's Hospital; Quanzhou Women's and Children's Hospital; The Maternal and Child Health Hospital of Guangxi Zhuang autonomous region; Xinjiang Children's Hospital; Shenzhen Maternity and Child Healthcare Hospital; Fujian Provincial Maternity and Children; Zhuhai Women and Children's Hospital; Children's Hospital Affiliated to Shandong University; Henan Maternal and Child Health Care Hospital; Gansu Provincial Maternal and Child Health Care Hospital
• Investigators: Study Chair: Wenhao Zhou, Doctor, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: High-Throughput Nucleotide Sequencing; Neonatal Sepsis; Metagenomics
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Toxemia; Neonatal Sepsis
• Other Study ID Numbers: CHFudanU_NNICU18

Drug and device information, study documents

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