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

Development Of A Non-Interventional Diagnostic Ngs-Based Assay Of Blood Samples Of Sepsis Patients For Rapid Bacterial Identification Based On Next Generation Sequencing.

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia; Bacteremia; Acute Pyelonephritis; Biliary Tract Infection
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of matching between the results of Next Generation Sequencing and the Standard-of-Care culture for patients with sepsis.	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.	7 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hellenic Institute for the Study of Sepsis
• Collaborators: The BioArte
• Investigators: Study Chair: Evangelos Giamarellos-Bourboulis, MD,PhD, Hellenic Institute for the Study of Sepsis

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Actual): March 14, 2024
• Study Completion (Actual): March 14, 2024

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Bacterial Infection; Next generation sequencing; Blood culture; Antimicrobial susceptibility testing; Time to pathogen identification
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Biliary Tract Diseases; Nephritis; Bile Duct Diseases; Nephritis, Interstitial; Pyelitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Bacteremia; Cholangitis; Pyelonephritis
• Other Study ID Numbers: BIOARTE

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