Optimization of Sepsis Therapy Based on Patient-specific Digital Precision Diagnostics
DigiSep
1 other identifier
interventional
410
1 country
22
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable sepsis
Started Mar 2022
Typical duration for not_applicable sepsis
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 21, 2020
CompletedFirst Posted
Study publicly available on registry
October 1, 2020
CompletedStudy Start
First participant enrolled
March 16, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 23, 2024
CompletedAugust 24, 2025
August 1, 2025
2 years
September 21, 2020
August 18, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk-Score
DOOR/RADAR-score \[points\], (min. 1, max. 5), a lower score indicates a better outcome
28 days
Secondary Outcomes (12)
Disease severity
at 90 and 180 days
Disease severity
at 28, 90, and 180 days
Degree of organ dysfunction/-failure
at 28, 90, and 180 days
Degree of organ dysfunction/-failure
during 28 days
Degree of organ dysfunction/-failure
at 28, 90, and 180 days
- +7 more secondary outcomes
Study Arms (2)
1
ACTIVE COMPARATORStandard diagnostics
2
EXPERIMENTALStandard diagnostics + NGS
Interventions
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
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
Eligibility Criteria
You may qualify if:
- All patients who develop sepsis or septic shock within \< 24 h in accordance with the new sepsis definition (Sepsis-3) in the above-mentioned participating centers and consent to participation in the study will be included.
- Written consent by the study participant or a legally appointed representative
- Age \>18 years
- Sepsis:
- Life-threatening organ dysfunction due to a dysregulated immune response on the basis of a suspected or proven infection
- Detection of organ dysfunction indicated by SOFA score of ≥ 2 points Alternative:
- Change of the quick (q) SOFA score of 2 points as an indication of a sepsis
- Or septic shock:
- Persistent hypotension despite adequate volume substitution, which necessitates the use of vasopressors, to maintain an arterial medium pressure of \> 65 mmHg
- Serum lactate \> 2 mmol/l (18 mg/dl)
You may not qualify if:
- Age \< 18 years
- Refusal to participate in the study
- Palliative therapy approach
- Patients who have already been included in the study but require re-admission to the intensive care unit cannot be included a second
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital, Essenlead
- Noscendo GmbH, Germanycollaborator
- Health Economics and Health Care Management, Bielefeld Universitycollaborator
- Institute of Medical Biometry and Informatics, University of Heidelbergcollaborator
- Coordination Centre for Clinical Trials (KKS), University of Heidelbergcollaborator
- Department of Infectious Diseases, University Hospital Essencollaborator
- Center for Infectious Diseases and Infection Control, Jena University Hospitalcollaborator
- Department of Anesthesiology, Heidelberg University Hospitalcollaborator
- AOK Rheinland/Hamburgcollaborator
- Barmer Health Insurance, Germanycollaborator
- Techniker Health Insurance, Germanycollaborator
Study Sites (22)
University Hospital Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
Heidenheim Hospital
Heidenheim, Baden-Wurttemberg, Germany
Konstanz Hospital
Konstanz, Baden-Wurttemberg, Germany
University Hospital Tübingen
Tübingen, Baden-Wurttemberg, Germany
University Hospital Ulm
Ulm, Baden-Wurttemberg, Germany
University Hospital TU München
München, Bavaria, Germany
University Hospital Regensburg
Regensburg, Bavaria, Germany
University Hospital Würzburg
Würzburg, Bavaria, Germany
Klinik Evangelisches Krankenhaus Luckau gGmbH
Luckau, Brandenburg, Germany
University Hospital Frankfurt
Frankfurt am Main, Hesse, Germany
Helios Dr. Horst Schmidt Hospital
Wiesbaden, Hesse, Germany
University Hospital Göttingen
Göttingen, Lower Saxony, Germany
University Hospital Hannover (MHH)
Hanover, Lower Saxony, Germany
University Hospital Rostock
Rostock, Mecklenburg-Vorpommern, Germany
University Hospital Aachen
Aachen, North Rhine-Westphalia, Germany
Klinik Evangelisches Krankenhaus Bethel gGmbH Bielefeld
Bielefeld, North Rhine-Westphalia, Germany
University Hospital Bonn
Bonn, North Rhine-Westphalia, Germany
University Hospital Köln
Cologne, North Rhine-Westphalia, Germany
University Hospital Düsseldorf
Düsseldorf, North Rhine-Westphalia, Germany
University Hospital Essen
Essen, North Rhine-Westphalia, Germany
University Hospital Leipzig
Leipzig, Saxony, Germany
University Hospital Charité
Berlin, State of Berlin, Germany
Related Publications (1)
Brenner T, Skarabis A, Stevens P, Axnick J, Haug P, Grumaz S, Bruckner T, Luntz S, Witzke O, Pletz MW, Ruprecht TM, Marschall U, Altin S, Greiner W, Berger MM; TIFOnet Critical Care Trials Group. Optimization of sepsis therapy based on patient-specific digital precision diagnostics using next generation sequencing (DigiSep-Trial)-study protocol for a randomized, controlled, interventional, open-label, multicenter trial. Trials. 2021 Oct 18;22(1):714. doi: 10.1186/s13063-021-05667-x.
PMID: 34663439DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Thorsten Brenner, MD
Department of Anesthesiology, University Hospital Essen
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 21, 2020
First Posted
October 1, 2020
Study Start
March 16, 2022
Primary Completion
March 28, 2024
Study Completion
April 23, 2024
Last Updated
August 24, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
Researchers with access to data are limited to the project partners involved. Researchers will receive pseudonymized data sets for data evaluations. A prerequisite for the transfer of the data to the project partners is the written consent of the patients.