Optimization of Sepsis Therapy Based on Patient-specific Digital Precision Diagnostics

Summary

Sepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. 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, the concept of plasmatic detection of circulating, free DNA employing next-generation sequencing (NGS) has shown to be suitable for the detection of disease-causing pathogens in patients with bloodstream infections.

The DigiSep-Trial is a randomized, controlled, interventional, multicenter trial to characterize the effect of the combination of NGS-based digital precision diagnostics, standard-of-care microbiological analyses and optional expert exchanges compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis / septic shock. The study examines in 410 patients (n = 205 per arm) with sepsis / septic shock whether the so-called DOOR-RADAR (Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) inpatient admission time, (2) consumption of antibiotics, (3) mortality and (4) acute renal failure (ARF)) can be significantly improved, by application of an additional NGS-based diagnostic concept. We also aim to investigate whether the new diagnostic procedure is cost-effective. It is postulated that the inpatient admission time, mortality rate, incidence of ARF, the duration of antimicrobial therapy as well as the costs of complications and outpatient aftercare can be reduced. Moreover, a significant improvement in the quality of life (QoL) of the affected patients can be expected.

Extensive preparatory work suggests that NGS-based diagnostics have higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. This preliminary work for the DigiSep-Trial with the help of an interventional study design provides the optimal basis to establish this new concept as part of the national standard based on the best possible evidence.

Conditions

• Sepsis
• Septic Shock

Interventions

DIAGNOSTIC_TEST

Standard diagnostics

Standard diagnostics (Microbial diagnostics by means of standard culture methods + optional consultation of experts in the field of infectious diseases) within the first 72 h after diagnosis of sepsis / septic shock

DIAGNOSTIC_TEST

Next Generation Sequencing (NGS)

Standard diagnostics + NGS (Microbial diagnostics using standard culture methods + Next Generation Sequencing + optional consultation of experts in the field of infectious diseases) within the first 72 h after diagnosis of sepsis / septic shock

Sponsors & Collaborators

• Noscendo GmbH, Germany

  collaborator UNKNOWN

• Health Economics and Health Care Management, Bielefeld University

  collaborator UNKNOWN

• Institute of Medical Biometry and Informatics, University of Heidelberg

  collaborator UNKNOWN

• Coordination Centre for Clinical Trials (KKS), University of Heidelberg

  collaborator UNKNOWN

• Department of Infectious Diseases, University Hospital Essen

  collaborator UNKNOWN

• Center for Infectious Diseases and Infection Control, Jena University Hospital

  collaborator UNKNOWN

• Department of Anesthesiology, Heidelberg University Hospital

  collaborator UNKNOWN

• AOK Rheinland/Hamburg

  collaborator INDUSTRY

• Barmer Health Insurance, Germany

  collaborator UNKNOWN

• Techniker Health Insurance, Germany

  collaborator UNKNOWN

• University Hospital, Essen

  lead OTHER

Principal Investigators

• Thorsten Brenner, MD · Department of Anesthesiology, University Hospital Essen

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-16

Primary Completion

2024-03-28

Completion

2024-04-23

Countries

• Germany

Study Locations