BIOARTE: NGS-Based Assay of Blood Samples of Sepsis Patients for Rapid Bacterial Identification

Sponsor

Hellenic Institute for the Study of Sepsis (Other)

Overall Status

Recruiting

CT.gov ID

NCT06141395

Collaborator

The BioArte (Other)

100

Enrollment

Locations

11.5

Anticipated Duration (Months)

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia Acute Pyelonephritis Bacteremia Biliary Tract Infection	Diagnostic Test: NGS-based assay for bacterial identification

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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.

Actual Study Start Date :

Nov 16, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Patients with an infection Patients with high suspicion of infection with at least one sign of the quick Sequential Organ Failure Assessment (qSOFA) score	Diagnostic Test: NGS-based assay for bacterial identification A total volume of 26ml of whole blood will be sampled from each enrolled patient for three consecutive days. This will be used for Standard-of-Care (SoC) culture and Next Generation Sequencing (NGS), for identification of circulating microorganisms.

Arm

Intervention/Treatment

Patients with an infection

Patients with high suspicion of infection with at least one sign of the quick Sequential Organ Failure Assessment (qSOFA) score

Diagnostic Test: NGS-based assay for bacterial identification

A total volume of 26ml of whole blood will be sampled from each enrolled patient for three consecutive days. This will be used for Standard-of-Care (SoC) culture and Next Generation Sequencing (NGS), for identification of circulating microorganisms.

Outcome Measures

Primary Outcome Measures

The rate of matching between the results of Next Generation Sequencing and the Standard-of-Care culture for patients with sepsis. [7 days]
This will be done by assessing the sensitivity, the specificity, the positive predictive value and the negative predictive value of Next Generation Sequencing and Standard-of-Care. For the analysis of this diagnostic performance, the results of the SoC cultures will be considered the "gold standard" for comparisons.

Secondary Outcome Measures

Difference in time to identification of the bacterial pathogen between Next Generation Sequencing and the Standard-of-Care culture [7 days]
The time from start of incubation until final identification will be recorded and compared between the two methods.
Difference in time to Antibiotic Susceptibility Testing between Next Generation Sequencing and the Standard-of-Care culture [7 days]
The time from start of incubation until the Antibiotic Susceptibility Testing will be recorded and compared between the two methods.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	4th Department of Internal Medicine,"Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School	Chaïdári	Attiki	Greece	12462
2	1st Department of Internal Medicine, General Hospital of Eleusis THRIASIO	Athens		Greece
3	3rd University Department of Internal Medicine, General Hospital of Chest Diseases of Athens SOTIRIA	Athens		Greece
4	3rd Department of Internal Medicine, General Hospital of Nikaia AGIOS PANTELEIMON	Nikaia		Greece