1. Designing phase 3 sepsis trials: application of learned experiences from critical care trials in acute heart failure
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Oliver Hartmann, Mathias Schroedter, John C. Marshall, Roger J. Lewis, Gernot Marx, Frauke Hein, Pierre-François Laterre, Joachim Struck, James A. Russell, Anne Louise Kjølbye, Peter Radermacher, Greet Van den Berghe, Paul Scigalla, Luciano Gattinoni, Mehmet Yilmaz, Michael O. Harhay, Etienne Gayat, Wendy Gattis Stough, Derek C. Angus, Andreas Bergmann, Alexandre Mebazaa, Matthieu Legrand, HAL UPMC, Gestionnaire, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of British Columbia (UBC), Adrenomed AG, Università degli Studi di Milano = University of Milan (UNIMI), University of Pennsylvania, Ferring Pharmaceuticals A/S, Harbor UCLA Medical Center [Torrance, Ca.], University of Toronto, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Universitätsklinikum Ulm - University Hospital of Ulm, Campbell University College, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Cumhuriyet Universitesi, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), UCL - (SLuc) Service de soins intensifs, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, [Mebazaa, Alexandre] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France -- [Mebazaa, Alexandre] AP HP, INSERM, U942, Paris, France -- [Mebazaa, Alexandre] Hop Univ St Louis Lariboisiere, AP HP, Dept Anesthesia & Crit Care, Paris, France -- [Laterre, Pierre Francois] Catholic Univ Louvain, St Luc Univ Hosp, Dept Crit Care Med, B-1200 Brussels, Belgium -- [Russell, James A.] Univ British Columbia, Ctr Heart Lung Innovat, St Pauls Hosp, Vancouver, BC V5Z 1M9, Canada -- [Russell, James A.] Univ British Columbia, St Pauls Hosp, Div Crit Care Med, Vancouver, BC V5Z 1M9, Canada -- [Bergmann, Andreas -- Hartmann, Oliver -- Hein, Frauke -- Schroedter, Mathias -- Scigalla, Paul -- Struck, Joachim] Adrenomed AG, Hennigsdorf, Germany -- [Gattinoni, Luciano] Univ Milan, Fdn IRCCS Ca Granda, Osped Maggiore Policlin, Milan, Italy -- [Gayat, Etienne] Univ Paris Diderot, Hop Univ St Louis Lariboisiere, AP HP, Dept Anesthesie Reanimat SMUR,INSERM,UMR 942, Paris, France -- [Harhay, Michael O.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Div Epidemiol, Philadelphia, PA 19104 USA -- [Kjolbye, Anne Louise] Ferring Pharmaceut, Copenhagen, Denmark -- [Legrand, Matthieu] Univ Paris 07, St Louis Hosp, UMR S942, Dept Anesthesiol,Crit Care & Burn Unit, Paris, France -- [Lewis, Roger J.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA -- [Marshall, John C.] Univ Toronto, St Michaels Hosp, Dept Surg, Interdept Div Crit Care Med, Toronto, ON, Canada -- [Marx, Gernot] Univ Hosp RWTH Aachen, Dept Intens Care & Intermediate Care, Aachen, Germany -- [Radermacher, Peter] Univ Ulm Klinikum, Inst Anasthesiol Pathophysiol & Verfahrensentwick, Ulm, Germany -- [Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA -- [Van den Berghe, Greet] Katholieke Univ Leuven, Div Cellular & Mol Med, Clin Dept, Leuven, Belgium -- [Van den Berghe, Greet] Katholieke Univ Leuven, Div Cellular & Mol Med, Lab Intens Care Med, Leuven, Belgium -- [Yilmaz, Mehmet Birhan] Cumhuriyet Univ, Fac Med, Dept Cardiol, Sivas, Turkey -- [Angus, Derek C.] Univ Pittsburgh, Sch Hlth Sci, Clin & Translat Sci Inst, CRISMA Ctr,Dept Crit Care Med,McGowan Inst Regner, Pittsburgh, PA USA -- [Angus, Derek C.] Univ Pittsburgh, Sch Hlth Sci, Clin & Translat Sci Inst, Dept Hlth Policy & Management,McGowan Inst Regene, Pittsburgh, PA USA, Van den Berghe, Greet -- 0000-0002-5320-1362, YILMAZ, Mehmet Birhan -- 0000-0002-8169-8628, YILMAZ, MEHMET BIRHAN -- 0000-0002-8169-8628, Harhay, Michael -- 0000-0002-0553-674X, GAYAT, Etienne -- 0000-0002-3334-3849, Gattinoni, Luciano -- 0000-0001-5380-2494, Mebazaa, Alexandre -- 0000-0001-8715-7753, Università degli Studi di Milano [Milano] (UNIMI), University of Pennsylvania [Philadelphia], and Rheinisch-Westfälische Technische Hochschule Aachen (RWTH)
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medicine.medical_specialty ,Clinical Sciences ,Psychological intervention ,Heart failure ,Review ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Phase (combat) ,Sepsis ,03 medical and health sciences ,Clinical trials as topic ,0302 clinical medicine ,medicine ,030212 general & internal medicine ,Mortality ,Intensive care medicine ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Septic shock ,business.industry ,Organ dysfunction ,medicine.disease ,Multiple organ failure ,3. Good health ,Clinical trial ,Etiology ,medicine.symptom ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
WOS: 000373260700001, PubMed ID: 27034779, 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., NHLBI NIH HHS [F31 HL127947]
- Published
- 2016
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