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.

Conditions

• Sepsis
• Septic Shock

Intervention / Treatment

• Diagnostic Test: Standard diagnostics
• Diagnostic Test: Next Generation Sequencing (NGS)

Primary Outcome Measures

• Desirability of Outcome Ranking / Response Adjusted for Duration of Antibiotic Risk-Score (28 days)
  DOOR/RADAR-score \[points\], (min. 1, max. 5), a lower score indicates a better outcome

Countries

Germany

Locations and Investigators

• University Hospital Heidelberg, Heidelberg, Germany (Not yet recruiting)
  • Markus Weigand, MD
• Heidenheim Hospital, Heidenheim, Germany (Not yet recruiting)
  • Alexander Brinkmann, MD
• Konstanz Hospital, Konstanz, Germany (Not yet recruiting)
  • Wolfgang Krüger, MD
• University Hospital Tübingen, Tübingen, Germany (Not yet recruiting)
  • Peter Rosenberger, MD
• University Hospital Ulm, Ulm, Germany (Not yet recruiting)
  • Hendrik Bracht, MD
• University Hospital TU München, München, Germany (Not yet recruiting)
  • Kristina Fuest, MD
• University Hospital Regensburg, Regensburg, Germany (Not yet recruiting)
  • Diane Bitzinger, MD
• University Hospital Würzburg, Würzburg, Germany (Not yet recruiting)
  • Patrick Meybohm, MD
• Klinik Evangelisches Krankenhaus Luckau gGmbH, Luckau, Germany (Not yet recruiting)
  • Ulrike Jäkel, MD
• University Hospital Frankfurt, Frankfurt, Germany (Not yet recruiting)
  • Simone Lindau
• Helios Dr. Horst Schmidt Hospital, Wiesbaden, Germany (Not yet recruiting)
  • Tobias Bingold, MD
• University Hospital Rostock, Rostock, Germany (Not yet recruiting)
  • Tobias Schürholz, MD
• University Hospital Göttingen, Göttingen, Germany (Not yet recruiting)
  • Onnen Mörer, MD
• University Hospital Hannover (MHH), Hannover, Germany (Not yet recruiting)
  • Klaudiusz Suchodolski, MD
• University Hospital Aachen, Aachen, Germany (Not yet recruiting)
  • Lukas Martin, MD
• Klinik Evangelisches Krankenhaus Bethel gGmbH Bielefeld, Bielefeld, Germany (Not yet recruiting)
  • Friedhelm Bach, MD
• University Hospital Bonn, Bonn, Germany (Not yet recruiting)
  • Christian Putensen, MD
• University Hospital Düsseldorf, Düsseldorf, Germany (Not yet recruiting)
  • Timo Brandenburger, MD
• University Hospital Essen, Essen, Germany (Recruiting)
  • Thorsten Brenner, MD
• University Hospital Köln, Köln, Germany (Not yet recruiting)
  • Fabian Dusse, MD
• University Hospital Leipzig, Leipzig, Germany (Not yet recruiting)
  • Sirak Petros, MD
• University Hospital Charité, Berlin, Germany (Not yet recruiting)
  • Stefan Schaller, MD

Study Officials

• Thorsten Brenner, MD (Principal Investigator) — Department of Anesthesiology, University Hospital Essen