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
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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).
Source: Intensive Care Medicine
Authors: Thorsten Brenner, Annabell Skarabis, Stefan J. Schaller, Thilo von Groote, Christian Putensen, Ulf Günther, Martin Sauer, Sebastian O. Decker, Fabian Dusse, Manfred Weiss, Klaudiusz Suchodolski, Tim-Philipp Simon, Peter Rosenberger, Onnen Moerer, Matthias Unterberg, Jens-Christian Schewe, Hendrik Bracht, Selina Hutzl, Manuel Feißt, Ursula Marschall, Patrick Brandenburg, Philip Stevens, Juliana Schmidt, Mathias W. Pletz, Marc M. Berger, on behalf of the German Society of Anaesthesiology and Intensive Care (GSAIC) Trials Group, Jens Brands, Alberto Antinoro, Linus O. Warner, Markus A. Weigand, Dominique M. Hart, Gernot Marx, Jana Mossanen, Thomas Breuer, Helene Häberle, Kristina Nitzsche, Paul Thalmann, Jolanda Brezinski, Joachim Saam, Silke Grumaz, Maren Steinmann, Maxime Gaasch, Bastian Pasieka, Ulrike Jaekel, Timo Brandenburger, Friedhelm Bach, Haitham Mutlak, Stefan Utzolino, Wolfgang A. Krueger, Stefan Hagel, Christian Lanckohr
Institutions: Essen University Hospital, University of Duisburg-Essen, Humboldt-Universität zu Berlin, Medical University of Vienna, Charité - Universitätsmedizin Berlin, University Hospital Münster, University of Bonn, University Hospital Bonn, Carl von Ossietzky Universität Oldenburg, University Medical Center Groningen, Klinikum Oldenburg, Klinikum Magdeburg, University Hospital Magdeburg, Heidelberg University, University of Cologne, University Hospital Cologne, University of Augsburg, Universität Ulm, University Hospital Ulm, Medizinische Hochschule Hannover, RWTH Aachen University, University of Tübingen, Universitätsmedizin Göttingen, University of Göttingen, Universitätsklinikum Knappschaftskrankenhaus Bochum, LWL-Universitätsklinikum Bochum, Ruhr University Bochum, Universitätsmedizin Rostock, University of Rostock, Bielefeld University, Jena University Hospital, Center for Sepsis Control and Care, Friedrich Schiller University Jena, Klinikum Ludwigsburg
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W7166693551