Evaluation of Droplet Digital PCR Rapid Detection Method and Precise Diagnosis and Treatment for Suspected Sepsis

Sepsis is a significant public health concern worldwide, with high morbidity and mortality. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures may represent a promising alternative. In particular, droplet digital PCR (ddPCR) is a novel one-step PCR assay that achieves higher accuracy and sensitivity in detecting causing pathogens in patients with bloodstream infections.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Diagnostic test: droplet digital PCR method; Diagnostic test: blood culture

• Study Type: Interventional
• Enrollment (Actual): 1032
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Hunan
    • Changsha, Hunan, China, 410013
      • Xiangya Hospital Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210001
      • Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine
    • Wuxi, Jiangsu, China, 214016
      • Wuxi No.5 People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200233
      • Shanghai Sixth People's Hospital
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 201100
      • Minhang Branch of Ruijin Hospital
  • Zhejiang
    • Rui'an, Zhejiang, China, 325200
      • Zhejiang Rui'an People's Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1.18 years or older

2.Meet 2 of 4 sepsis criteria

1. Temperature > 38C or < 36C
2. Heart rate > 90 bpm
3. Respiratory rate >20 or PaCO2 <32mmHg

4. WBC >12000/µL or < 4000/µL or > 10% bands

   3.Hospitalized patients who have a diagnostic blood culture ordered as standard of care for suspected sepsis

   4.Informed Consent by patient or legal representative.

   Exclusion Criteria:

   1. Refusal to participate in the study or Failure to comply with treatment or follow-up time
   2. Known breastfeeding or pregnancy
   3. The researcher believes that there are any conditions (social or medical) that allow subjects to participate is unsafe. For example, severe anemia or high risk of bleeding,etc., which are not suitable for taking peripheral blood for testing
   4. Participating in other clinical studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: droplet digital PCR method; Pathogen detection by droplet digital PCR method as an adjunct to traditional microbiological assessments including blood culture	Diagnostic test: droplet digital PCR method; The droplet digital PCR method can detect nucleic acids from the most common pathogens (approximately 90%) responsible for BSIs according to Chinet2020 and takes about 4 hours to perform, reporting within the first 24h of suspected sepsis/septic shock.
Active Comparator: blood culture only; Pathogen detection by microbiological assessments including blood culture	Diagnostic test: blood culture; Blood culture is a conventional microbiological method of pathogen detection. Results from blood cultures are usually not available until 24 to 72 hours after sampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	The primary endpoint of estimated sensitivity will be determined by comparing positive blood culture results with the concomitantly collected ddPCR results from the prospective clinical specimens.	Up to 96 hours post blood collection
Specificity	The primary endpoint of estimated specificity will be determined by comparing negative blood culture results with the concomitantly collected ddPCR results from the prospective clinical specimens.	Up to 96 hours post blood collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the change to the targeted antimicrobial therapy		At time point of change to the targeted antimicrobial therapy, up to 96 hours post blood collection
Number of patients with targeted antimicrobial therapy		Up to the end of study participation, an average of 1 year
Time to identification of a potential pathogen		At time point of identification of a potential pathogen, up to 96 hours post blood collection
Duration of antimicrobials		Up to the end of study participation, an average of 1 year
Change in condition severity	The sequential organ failure assessment score (SOFA score), previously known as the sepsis-related organ failure assessment score, higher scores mean worse outcome.	Up to the end of study participation, an average of 1 year
Days in intensive care unit (ICU)		Up to the end of study participation, an average of 1 year
Ventilation duration in ICU (hours)		Up to the end of study participation, an average of 1 year
Days in hospital (from study inclusion)		Up to the end of study participation, an average of 1 year
All-cause death		Up to the end of study participation, an average of 1 year
Treatment costs		Up to the end of study participation, an average of 1 year
Quality of life of survivors after being discharged	EQ-5D, a standardised measure of health-related quality of life developed by the EuroQol Group.The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. The number of levels in these dimensions is 5 in the EQ-5D-5L. Higher levels mean worse health states.	Up to the end of study participation, an average of 1 year

Collaborators and Investigators

• Sponsor: Huashan Hospital

Publications and helpful links

General Publications

• Zhao Y, Lin K, Zhang H, Yuan G, Zhang Y, Pan J, Hong L, Huang Y, Ye Y, Huang L, Chen X, Liu J, Li X, He X, Yue Q, Zhang H, Zhou A, Zhuang Y, Chen J, Wu C, Zhou W, Cai F, Zhang S, Li L, Li S, Bian T, Li J, Yin J, Ruan Z, Xu S, Zhang Y, Chen J, Zhang Y, Han J, Su T, Tu F, Jiang L, Lei C, Du Q, Ai J, Zhang W. Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial. BMC Infect Dis. 2022 Jul 19;22(1):630. doi: 10.1186/s12879-022-07557-2.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2021
• Primary Completion (Actual): December 29, 2023
• Study Completion (Actual): December 29, 2023

Study Registration Dates

• First Submitted: November 25, 2021
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 13, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Digital Droplet PCR; Etiology Diagnose
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: PROGRESS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No