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

Study Overview
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Brief Summary
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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.

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

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Diagnostic Test: droplet digital PCR method
* Diagnostic Test: blood culture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 years or older 2.Meet 2 of 4 sepsis criteria Temperature > 38C or < 36C Heart rate > 90 bpm Respiratory rate >20 or PaCO2 <32mmHg 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: Refusal to participate in the study or Failure to comply with treatment or follow-up time Known breastfeeding or pregnancy 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 Participating in other clinical studies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: droplet digital PCR method<br>Pathogen detection by droplet digital PCR method as an adjunct to traditional microbiological assessments including blood culture | Diagnostic Test: droplet digital PCR method<br>* 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.<br>|
| Active Comparator: blood culture only<br>Pathogen detection by microbiological assessments including blood culture | Diagnostic Test: blood culture<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Digital Droplet PCR, Etiology Diagnose