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Purpose <p>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.</p> Methods <p>This randomized, controlled, interventional, open-label, multicenter trial was conducted in 24 intensive care units across Germany. The intervention group (<i>n</i> = 200) received mNGS diagnostics in addition to standard-of-care microbiology, compared with standard-of-care microbiology alone (control group; <i>n</i> = 189). The primary endpoint was the Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk (DOOR/RADAR) score.</p> Results <p>The DOOR/RADAR score was not significantly improved at 28&#xa0;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&#xa0;days; control group: 9.3 ± 10.6&#xa0;days; 95% CI − 5.03 to − 0.34) and faster shock resolution (intervention group: 6.9 ± 7.4&#xa0;days; control group: 8.8 ± 8.5&#xa0;days; 95% CI − 3.75 to − 0.04). Health-related quality of life at 90&#xa0;days (EQ-5D-5L) was improved in the intervention group (0.312 ± 0.386) compared with the control group (0.208 ± 0.373; <i>p</i> = 0.047). In the subgroup with available claims data (33.2% of participating patients), healthcare costs over 180&#xa0;days did not differ.</p> Conclusion <p>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).</p> Visual abstract <p></p>

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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

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  • 发表日期：

    2026年6月30日

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  • 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,
  • 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

摘要

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).

Visual abstract