Designing phase 3 sepsis trials: Application of learned experiences from critical care trials in acute heart failure

Alexandre Mebazaa, Pierre François Laterre, James A. Russell, Andreas Bergmann, Luciano Gattinoni, Etienne Gayat, Michael O. Harhay, Oliver Hartmann, Frauke Hein, Anne Louise Kjolbye, Matthieu Legrand, Roger J. Lewis, John C. Marshall, Gernot Marx, Peter Radermacher, Mathias Schroedter, Paul Scigalla, Wendy Gattis Stough, Joachim Struck, Greet Van den BergheMehmet Birhan Yilmaz, Derek C. Angus

Research output: Contribution to journalReview article

Abstract

Substantial attention and resources have been directed to improving outcomes of patients with critical illnesses, in particular sepsis, but all recent clinical trials testing various interventions or strategies have failed to detect a robust benefit on mortality. Acute heart failure is also a critical illness, and although the underlying etiologies differ, acute heart failure and sepsis are critical care illnesses that have a high mortality in which clinical trials have been difficult to conduct and have not yielded effective treatments. Both conditions represent a syndrome that is often difficult to define with a wide variation in patient characteristics, presentation, and standard management across institutions. Referring to past experiences and lessons learned in acute heart failure may be informative and help frame research in the area of sepsis. Academic heart failure investigators and industry have worked closely with regulators for many years to transition acute heart failure trials away from relying on dyspnea assessments and all-cause mortality as the primary measures of efficacy, and recent trials have been designed to assess novel clinical composite endpoints assessing organ dysfunction and mortality while still assessing all-cause mortality as a separate measure of safety. Applying the lessons learned in acute heart failure trials to severe sepsis and septic shock trials might be useful to advance the field. Novel endpoints beyond all-cause mortality should be considered for future sepsis trials.

Original languageEnglish
Article number24
JournalJournal of Intensive Care
Volume4
Issue number1
DOIs
Publication statusPublished - 2016

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Keywords

  • Clinical trials as topic
  • Heart failure
  • Mortality
  • Multiple organ failure
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Mebazaa, A., Laterre, P. F., Russell, J. A., Bergmann, A., Gattinoni, L., Gayat, E., Harhay, M. O., Hartmann, O., Hein, F., Kjolbye, A. L., Legrand, M., Lewis, R. J., Marshall, J. C., Marx, G., Radermacher, P., Schroedter, M., Scigalla, P., Stough, W. G., Struck, J., ... Angus, D. C. (2016). Designing phase 3 sepsis trials: Application of learned experiences from critical care trials in acute heart failure. Journal of Intensive Care, 4(1), [24]. https://doi.org/10.1186/s40560-016-0151-6