Effects of a clinical metagenomics intervention on clinical outcomes, healthcare costs, and health-related quality of life in patients with sepsis or septic shock: results of the randomized-controlled DigiSep trial

PURPOSE: Early pathogen detection is crucial in sepsis. We hypothesized that detection of microbial circulating cell-free DNA by metagenomic next-generation sequencing (mNGS) improves clinical outcomes and health-related quality of life without increasing healthcare costs. METHODS: This randomized, controlled, interventional, open-label, multicenter trial was conducted in 24 intensive care units across Germany. The intervention group (n = 200) received mNGS diagnostics in addition to standard-of-care microbiology, compared with standard-of-care microbiology alone (control group; n = 189). The primary endpoint was the Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk (DOOR/RADAR) score. RESULTS: The DOOR/RADAR score was not significantly improved at 28 days after sepsis onset (intervention group: 3.21 ± 1.54; control group: 3.49 ± 1.51; 95% CI - 0.58 to 0.03). However, other secondary endpoints were improved, including a reduced duration of mechanical ventilation (intervention group: 6.6 ± 9.4 days; control group: 9.3 ± 10.6 days; 95% CI - 5.03 to - 0.34) and faster shock resolution (intervention group: 6.9 ± 7.4 days; control group: 8.8 ± 8.5 days; 95% CI - 3.75 to - 0.04). Health-related quality of life at 90 days (EQ-5D-5L) was improved in the intervention group (0.312 ± 0.386) compared with the control group (0.208 ± 0.373; p = 0.047). In the subgroup with available claims data (33.2% of participating patients), healthcare costs over 180 days did not differ. CONCLUSION: The DOOR/RADAR score as primary endpoint was not significantly improved by mNGS. Exploratory secondary analyses revealed improvements in secondary endpoints. (Funding: German Innovation Fund; ClinicalTrials.gov number, NCT04571801, registration: 25.8.2020).

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Publication Details

Journal
Intensive Care Medicine
Published
2026-06-30
DOI
https://doi.org/10.1007/s00134-026-08521-3
Primary Topic
Sepsis Diagnosis and Treatment
Type
article
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article

Effects of a clinical metagenomics intervention on clinical outcomes, healthcare costs, and health-related quality of life in patients with sepsis or septic shock: results of the randomized-controlled DigiSep trial

Bastian Pasieka, Klaudiusz Suchodolski, Annabell Skarabis, Matthias Unterberg et al.
Intensive Care Medicine
Sepsis Diagnosis and Treatment
article

Effects of a clinical metagenomics intervention on clinical outcomes, healthcare costs, and health-related quality of life in patients with sepsis or septic shock: results of the randomized-controlled DigiSep trial

Bastian Pasieka, Klaudiusz Suchodolski, Annabell Skarabis, Matthias Unterberg, Patrick Brandenburg, Philip Stevens, Jens Brands, Maren Steinmann, Timo Brandenburger, Christian Lanckohr, Thorsten Brenner, P B Rosenberger, Haitham Mutlak, Stefan Utzolino, Fabian Dusse, M R Weigand, Jolanda Brezinski, Maxime Gaasch, T M Breuer, Ulrike Jaekel, Jens‐Christian Schewe, Friedhelm Bach, Wolfgang A. Krueger, S Schaller, Manuel Feißt, Hendrik Bracht, Silke Grumaz, Paul Thalmann, Helene Häberle, Tim-Philipp Simon, Linus Warner, Manfred Weiss, Juliana Schmidt, Sebastian O. Decker, Marc M. Berger, Thilo von Groote, Joachim Saam, Martin Sauer, on behalf of the German Society of Anaesthesiology and Intensive Care (GSAIC) Trials Group, Stefan Hagel, Selina Hutzl, Mathias W. Pletz, Gernot Marx, Kristina Nitzsche, Ursula Marschall, Alberto Antinoro, Jana Mossanen, Ulf Günther, Dominique M. Hart, Christian Putensen, Onnen Moerer
article en

Abstract

PURPOSE: Early pathogen detection is crucial in sepsis. We hypothesized that detection of microbial circulating cell-free DNA by metagenomic next-generation sequencing (mNGS) improves clinical outcomes and health-related quality of life without increasing healthcare costs. METHODS: This randomized, controlled, interventional, open-label, multicenter trial was conducted in 24 intensive care units across Germany. The intervention group (n = 200) received mNGS diagnostics in addition to standard-of-care microbiology, compared with standard-of-care microbiology alone (control group; n = 189). The primary endpoint was the Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk (DOOR/RADAR) score. RESULTS: The DOOR/RADAR score was not significantly improved at 28 days after sepsis onset (intervention group: 3.21 ± 1.54; control group: 3.49 ± 1.51; 95% CI - 0.58 to 0.03). However, other secondary endpoints were improved, including a reduced duration of mechanical ventilation (intervention group: 6.6 ± 9.4 days; control group: 9.3 ± 10.6 days; 95% CI - 5.03 to - 0.34) and faster shock resolution (intervention group: 6.9 ± 7.4 days; control group: 8.8 ± 8.5 days; 95% CI - 3.75 to - 0.04). Health-related quality of life at 90 days (EQ-5D-5L) was improved in the intervention group (0.312 ± 0.386) compared with the control group (0.208 ± 0.373; p = 0.047). In the subgroup with available claims data (33.2% of participating patients), healthcare costs over 180 days did not differ. CONCLUSION: The DOOR/RADAR score as primary endpoint was not significantly improved by mNGS. Exploratory secondary analyses revealed improvements in secondary endpoints. (Funding: German Innovation Fund; ClinicalTrials.gov number, NCT04571801, registration: 25.8.2020).

Intensive Care Medicine
University Medical Center Groningen (NL), Technische Hochschule Augsburg (DE), University of Augsburg (DE), Hanze University of Applied Sciences (NL), Universität Ulm (DE), Bielefeld University (DE), Hochschule Bielefeld (DE), Heidelberg University (DE), University Hospital Bonn (DE), University Hospital Heidelberg (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Zimmer Biomet (Germany) (DE), University Hospital Münster (DE), Evangelisches Krankenhaus Bielefeld (DE), Klinikum Magdeburg (DE), BARMER GEK (DE), Klinikum Oldenburg (DE), Universitätsklinikum Knappschaftskrankenhaus Bochum (DE), Universitätsmedizin Göttingen (DE), National Health Insurance Fund (RS), Essen University Hospital (DE), Klinikum Bielefeld (DE), Jena University Hospital (DE), University Hospital Magdeburg (DE), Klinikum Ludwigsburg (DE), University Hospital Cologne (DE), University Hospital Ulm (DE), University of Rostock (DE), University of Duisburg-Essen (DE), Medical University of Vienna (AT), Friedrich Schiller University Jena (DE), University of Tübingen (DE), RWTH Aachen University (DE), Bethel University (US)
Universitätsklinikum Essen, Gemeinsame Bundesausschuss
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Sepsis Diagnosis and Treatment
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