Abstract
Purpose
To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock.
Methods
We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences.
Results
All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS.
Conclusions
Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials.
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Acknowledgments
Coordinator center staff for each trial (in alphabetical order): ProCESS: T. Eaton, E. Gimbel, K. Wofford. ARISE: A. Jovanovska, G. Syres, D. Rajbhandari. ProMISe: R. Jahan, H. Muskett, S. Power, J. Tan. This study was supported by (ProCESS) National Institute of Health P50GM076659 and GM076659-S1, (ARISE) National Health and Medical Research Council Project Grant 491075, (ProMISe) National Institute for Health Research Health Technology Assessment programme HTA 07/37/47.
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Additional information
This article was written by the ProCESS/ARISE/ProMISe Methodology Writing Committee, on behalf of the ProCESS investigators, the ARISE investigators for the ANZICS Clinical Trials Group, and the ProMISe investigators. The members of the Committee are listed in the Appendix. The work was conducted by the University of Pittsburgh, the Australian and New Zealand Intensive Care Research Centre, Monash University, and the Intensive Care National Audit and Research Centre.
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Appendix: members of ProCESS/ARISE/ProMISe methodology writing committee
Appendix: members of ProCESS/ARISE/ProMISe methodology writing committee
ProCESS (after Chair, authors are listed alphabetically): David T. Huang, MD, MPH (Chair)1,2,3, Derek C. Angus, MD, MPH1,2, Amber Barnato, MD1,4, MPH, Scott R. Gunn, MD2,3, John A. Kellum, MD1,2, Diana K. Stapleton, RN, BS1,2, Lisa A. Weissfeld, PhD1,5, MS, Donald M. Yealy, MD3.
ARISE (after first two, authors are listed alphabetically): Sandra L. Peake, BM BS, BSc (Hons) PhD, FCICM11,17,18, Anthony Delaney MBBS MSc FCICM, FACEM12,13, Rinaldo Bellomo MBBS, MD, FRACP, FJFICM6,7,8,9, Peter Cameron MBBS, MD, FACEM10,11, Alisa Higgins MPH, BPhysio (Hons)14, Anna Holdgate, MBBS (Hons), MMed, FACEM15,16, Belinda Howe RN, CCCert, BAppSc (Nursing)14, Steven A. Webb MBBS, PhD, FRACP, FCICM, MPH14,19,20, Patricia Williams RGN, BN Int. Care17,18.
ProMISe: Tiffany M. Osborn, MD, MPH21, Paul R. Mouncey MSc21, David A. Harrison PhD21, Sheila E. Harvey PhD21, Kathryn M. Rowan, PhD21.
1. The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center.
2. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
3. Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA.
4. Department of Internal Medicine, Division of General Internal Medicine, Center for Research on Health Care.
5. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
6. School of Medicine, University of Melbourne, Melbourne, VIC, Australia.
7. School of Medicine, Monash University, Melbourne, VIC, Australia.
8. Howard Florey Institute, Melbourne University, Melbourne, VIC, Australia.
9. Department of Intensive Care Medicine, Austin Hospital, Heidelberg, VIC, Australia.
10. Department of Emergency Medicine, Alfred Hospital, Melbourne, VIC, Australia.
11. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventative Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
12. Intensive Care Unit, Royal North Shore Hospital, Sydney, NSW, Australia.
13. Northern Clinical School, Sydney Medical School, University of Sydney, NSW, Australia.
14. Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
15. South West Clinical School, University of New South Wales, Sydney, NSW, Australia.
16. Department of Emergency Medicine, Liverpool Hospital, Sydney, NSW, Australia.
17. Department of Intensive Care Medicine, The Queen Elizabeth Hospital, School of Medicine, Adelaide, SA, Australia.
18. Discipline of Acute Care Medicine, Faculty of Health Science, University of Adelaide, SA, Australia.
19. Intensive Care Unit, Royal Perth Hospital, Perth, WA, Australia.
20. School of Medicine, Pharmacology and Public Health, University of Western Australia, Perth, WA, Australia.
21. Intensive Care National Audit and Research Centre (ICNARC), Napier House, 24 High Holborn, London, UK.
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The ProCESS/ARISE/ProMISe Methodology Writing Committee. Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe. Intensive Care Med 39, 1760–1775 (2013). https://doi.org/10.1007/s00134-013-3024-7
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DOI: https://doi.org/10.1007/s00134-013-3024-7
Keywords
- Septic shock
- Clinical trial
- Severe sepsis
- Early goal-directed therapy
- Study design
- Methodology