Droplet Digital PCR Combines With Transcriptome Analysis in Early Warning of Sepsis in the Emergency Department

Clinical Evaluation of Droplet Digital Polymerase Chain Reaction in Combination With Transcriptome Analysis in Early Warning of Sepsis in the Emergency Department: A Multicenter Prospective Observational Study

Rapid identification of pathogens and early warning of host response are key to improve the prognosis of sepsis. Establishing a comprehensive identification system based on pathogen identification and host immune status is an effective way to achieve early warning stratification of patients with infections in the emergency department. This prospective multicenter clinical study will combine droplet digital PCR (ddPCR) and transcriptomic molecular target assay for validation in patients with suspected sepsis in the emergency department. The purpose is to (1) compare the efficacy of ddPCR with blood culture for early diagnosis and prognosis; (2) assess the diagnostic value of transcriptomic molecular targets based on 29 messenger RNA for the presence or absence of infection as well as infectious agents, and to evaluate their efficacy for prognosis; and (3) assess the diagnostic and therapeutic monitoring value of ddPCR combined with transcriptome analysis methods.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Emergent Infections, Treatment
• Intervention / Treatment: Diagnostic test: Droplet digital PCR

Detailed Description

Rapid identification of pathogens and early warning of host response are key to improve the prognosis of sepsis. Establishing a comprehensive identification system based on pathogen identification and host immune status is an effective way to achieve early warning stratification of patients with infections in the emergency department. Therefore, based on our preliminary single-center study, this prospective multicenter clinical study will combine droplet digital PCR (ddPCR) and transcriptomic molecular target assay for validation in patients with suspected sepsis in the emergency department. The purpose is to (1) compare the efficacy of ddPCR with blood culture for early diagnosis and prognosis; (2) assess the diagnostic value of transcriptomic molecular targets based on 29 messenger RNA for the presence or absence of infection as well as infectious agents, and to evaluate their efficacy for prognosis; and (3) assess the diagnostic and therapeutic monitoring value of ddPCR combined with transcriptome analysis methods. In a word, this study will be undertaken to assess the diagnostic and therapeutic monitoring value of early warning models for sepsis in emergency department and to promote them to improve the identification ability of emergency infections.

• Study Type: Observational
• Enrollment (Estimated): 360

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Prospective inclusion of patients with suspected sepsis with MSS ≥ 2 in the emergency department of Shanghai East Hospital, Shanghai Pudong New District Zhoupu Hospital, Shanghai Pudong New District Gongli Hospital, Shanghai Pudong Hospital and Shanghai Punan Hospital Hospital, Shanghai Pudong Hospital, Shanghai Pudong New Area Hospital and Shanghai Pudong New Area Punan Hospital. The patients will be randomized by stratified grouping and assigned to two parallel groups in the ratio of 5:1.

Description

Inclusion Criteria:

• age ≥ 18 years, regardless of sex
• MSS≥2 score
• written informed consent obtained

Exclusion Criteria:

• Age < 18 years, regardless of sex
• Patient's ICU length of stay <24 hours
• Malignant tumor, HIV patients or any terminal-stage disease
• Known pregnancy or lactation
• Participation in other clinical trials
• Inadequate clinical information or missing experimental data
• No signed informed consent obtained

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental group; The experimental group will recruit 300 participants undergoing blood culture, droplet digital PCR and transcriptome analysis.	Diagnostic test: Droplet digital PCR; Droplet digital PCR has potential in resolving polymicrobial infection because it simultaneously achieves unprecedented high sensitivity , high specificity, and absolute quantification without the need for a standard curve.; Other Names: Transcriptomic analysis
Control group; The control group will recruit 60 participants undergoing blood culture only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic efficiency of ddPCR combined with transcriptomic analysis in suspected sepsis	Diagnostic efficiency of ddPCR combined with transcriptomic analysis for suspected sepsis in the emergency medicine	7days
Prognostic value of ddPCR combined with transcriptomic analysis in suspected sepsis	Prognostic value of ddPCR combined with transcriptomic analysis for suspected sepsis in the emergency medicine	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day all-cause mortality rate	Evaluation of combined examination by ddPCR and transcriptomic analysis for the evaluation of the prognosis of the sepsis.	7 days
28-day all-cause mortality rate	Evaluation of combined examination by ddPCR and transcriptomic analysis for the evaluation of the prognosis of the sepsis.	28 days
90-day all-cause mortality rate	Evaluation of combined examination by ddPCR and transcriptomic analysis for the evaluation of the prognosis of the sepsis.	90 days
Antimicrobial Resistance and antibiotic application	Evaluation of combined examination by ddPCR and transcriptomic analysis for the the value of guiding clinical drug therapy.	7 days

Collaborators and Investigators

• Sponsor: Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: September 5, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Droplet digital PCR; Transcriptomic molecular target assay
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Toxemia; Emergencies
• Other Study ID Numbers: emergency medicine 20230824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data that underlie results in a publication
• IPD Sharing Time Frame: 3 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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