Clinical trial NCT06141395: NGS-Based Assay of Blood Samples of Sepsis Patients for Rapid Bacterial Identification
Official title: Development Of A Non-Interventional Diagnostic Ngs-Based Assay Of Blood Samples Of Sepsis Patients For Rapid Bacterial Identification Based On Next Generation Sequencing.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia
Acute Pyelonephritis
Bacteremia
Biliary Tract Infection
Keywords: Bacterial Infection
Antimicrobial susceptibility testing
Next generation sequencing
Blood culture
Time to pathogen identification
Lead sponsor: Hellenic Institute for the Study of Sepsis
Sponsor class: OTHER
Collaborators: name: The BioArte
First posted: 2023-11-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who meet all inclusion criteria and who do not meet any exclusion criterion will be enrolled in the study.

Brief summary: Rapid detection of microorganisms is a promising approach towards early administration of appropriate antibiotics for sepsis. This study aims to investigate the potential of a new NGS platform for the rapid diagnosis of circulating bacteria in blood.

Detailed description: Early start of antimicrobials is the cornerstone of management of critically ill patients. The appropriate time window for this early intervention may vary greatly, but it is considered to be one to 3 hours from hospital admission. However, the choice of the antimicrobials for early intervention relies on empirical selection and may several times be inappropriate due to the emergence of antimicrobial resistance. The only way to overcome this difficulty is guidance through early microbial identification and antibiotic susceptibility testing (AST). However, blood cultures are positive in almost 20% of critically ill patients and AST may delay as much as 72 hours.

This means that another type of approach is warranted which will tackle the major limitation of standard-of-care (SoC) microbiology, namely, the need to incubate whole blood into flasks enriched with growth media which necessitates subculturing once a blood flask turns positive. It is evident that rapid identification of the pathogen followed by AST using whole blood without the need of blood culture can be a major advance in the diagnostic field.

The present study is based on previous analysis of ethylenediaminetetraacetic acid (EDTA) whole blood coming from patients with known bloodstream infection. Next generation sequencing (NGS) of bacterial DNA extracted from whole blood managed to identify the correct pathogen. This study is aiming at the validation of this NGS -based assay in a broader number of patients.

Eligibility criteria: Inclusion Criteria:

* Age equal to or above 18 years.
* Both genders.
* Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent.
* Patients with high suspicion of infection with at least one sign of the quick SOFA score (i.e. one of mental confusion, more than 22 breaths per minute or systolic blood pressure less than 100mmHg).

Exclusion Criteria:

* Age below 18 years.
* Denial for written informed consent.
* Patients already receiving antibiotics.
* Pregnancy or lactation.

Primary outcomes:
measure: The rate of matching between the results of Next Generation Sequencing and the Standard-of-Care culture for patients with sepsis.
timeFrame: 7 days
Secondary outcomes:
measure: Difference in time to identification of the bacterial pathogen between Next Generation Sequencing and the Standard-of-Care culture
timeFrame: 7 days
measure: Difference in time to Antibiotic Susceptibility Testing between Next Generation Sequencing and the Standard-of-Care culture
timeFrame: 7 days
Other outcomes:
Locations:
city: Chaïdári
country: Greece
facility: 4th Department of Internal Medicine,"Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School
state: Attiki
city: Athens
country: Greece
facility: 1st Department of Internal Medicine, General Hospital of Eleusis THRIASIO
city: Athens
country: Greece
facility: 3rd University Department of Internal Medicine, General Hospital of Chest Diseases of Athens SOTIRIA
city: Nikaia
country: Greece
facility: 3rd Department of Internal Medicine, General Hospital of Nikaia AGIOS PANTELEIMON
Study officials:
affiliation: Hellenic Institute for the Study of Sepsis
name: Evangelos Giamarellos-Bourboulis, MD,PhD
role: STUDY_CHAIR
References: