TY - JOUR
T1 - Designing phase 3 sepsis trials
T2 - Application of learned experiences from critical care trials in acute heart failure
AU - Mebazaa, Alexandre
AU - Laterre, Pierre François
AU - Russell, James A.
AU - Bergmann, Andreas
AU - Gattinoni, Luciano
AU - Gayat, Etienne
AU - Harhay, Michael O.
AU - Hartmann, Oliver
AU - Hein, Frauke
AU - Kjolbye, Anne Louise
AU - Legrand, Matthieu
AU - Lewis, Roger J.
AU - Marshall, John C.
AU - Marx, Gernot
AU - Radermacher, Peter
AU - Schroedter, Mathias
AU - Scigalla, Paul
AU - Stough, Wendy Gattis
AU - Struck, Joachim
AU - Van den Berghe, Greet
AU - Yilmaz, Mehmet Birhan
AU - Angus, Derek C.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Clinical trials as topic
KW - Heart failure
KW - Mortality
KW - Multiple organ failure
KW - Sepsis
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U2 - 10.1186/s40560-016-0151-6
DO - 10.1186/s40560-016-0151-6
M3 - Review article
AN - SCOPUS:84991039521
VL - 4
JO - Journal of Intensive Care
JF - Journal of Intensive Care
SN - 2052-0492
IS - 1
M1 - 24
ER -