Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

Valery Likhvantsev, Ingrid Copland, David Stillo, Pavel Roshanov, Richard P Whitlock, Andre Lamy, Michael McGillion, Hector J Aguado, Pilar Paniagua Iglesisas, Jessica Vincent, Miriam de Nadal, Keyur Bhatt, Mikhail Kirov, Marat Abubakirov, Sabry Ayad, Chao Chia Cheong, William K K Wu, Toby Richards, P J Devereaux, Salim Yusuf, William McIntyre, Jessica Spence, Emily Belley-Cote, Gordon Guyatt, Pascal Alfonsi, Peter L Gross, Tomas VanHelder, John Eikelboom, Shirley Petit, Sadeesh Srinathan, Andrea Kurz, Bruce Biccard, Shrikant I Bangdiwala, Kumar Balasubramanian, Maria J Martínez Zapata, Denis Schmartz, Wojciech Szczeklik, Ydo V Kleinlugtenbelt, Sergey Efremov, Giovanni Landoni, Sandra N Ofori, Denis Xavier, C Y Wang, Amit X Garg, Flavia K Borges, Matthew T V Chan, Daniel Sessler, Vladimir V Lomivorotov, Kate Leslie, David Conen, Thomas W Painter, Kurtz Ruetzler, Mangala Rao, Sergey V Astrakov, Raja Jayaram, Carisi A Polanczyk, Edith Fleischmann, Michael K Wang, Vikas Tandon, Joel L Parlow, Maura Marcucci, Emmanuelle Duceppe, Ameen Patel, David Torres, Mohammed Amir, Christian S Meyhoff, Maria Wittmann, Timothy G Short

Journal: Trials 2022;23(1):101

PMID: 35101083

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Abstract

BACKGROUND

For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes.

METHODS

The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization.

DISCUSSION

Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Address: Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. [email protected].; Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. [email protected].; Population Health Research Institute, Hamilton, ON, Canada. [email protected].; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia, Australia.; Department of Anaesthesia, Royal Adelaide Hospital, Adelaide, South Australia, Australia.; Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.; Population Health Research Institute, Hamilton, ON, Canada.; Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Australia.; Department of Critical Care Medicine, Melbourne Medical School, University of Melbourne, Melbourne, Australia.; Department of Anesthesiology and Intensive Care, E. Meshalkin National Medical Research Center, Novosibirsk, Russia.; Department of Anesthesiology and Intensive Care, Novosibirsk State University, Novosibirsk, Russia.; Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA.; The Chinese University of Hong Kong, Hong Kong, China.; Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.; Iberoamerican Cochrane Centre-Public Health and Clinical Epidemiology Service, IIB Sant Pau, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.; Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; St. John's Medical College, Bangalore, India.; Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.; Saint Petersburg State University Hospital, Saint Petersburg, Russia.; Department of Orthopedic and Trauma Surgery, Deventer Ziekenhuis, Deventer, the Netherlands.; Jagiellonian University Medical College, Center for Intensive Care and Perioperative Medicine, Krakow, Poland.; CHU Brugmann, Université libre de Bruxelles, Brussels, Belgium.; Department of Medicine, Epidemiology and Biostatistics, Western University, London, ON, Canada.; Auckland City Hospital, Auckland, New Zealand.; University of Auckland, School of Health Sciences, Auckland, New Zealand.; Department of Anesthesiology, University Hospital, Bonn, Germany.; Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.; Shifa International Hospital (STMU), Islamabad, Pakistan.; Clinica Santa Maria, Santiago, Chile.; Universidad de Los Andes, Santiago, Chile.; Department of Medicine, Universite de Montreal, Montreal, QC, Canada.; Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital and Queen's University, Kingston, ON, Canada.; Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.; Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.; Cardiology Department, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; Nuffield Department of Anaesthetics, Clinical Neurosciences, University of Oxford, Oxford, UK.; City hospital No. 25, Novosibirsk, Russia.; Department of Anesthesiology, Novosibirsk State University, Novosibirsk, Russia.; Department of Anesthesia, McMaster University, Hamilton, ON, Canada.; Case Western Reserve University, Anesthesiology Institute, Cleveland Clinic - Fairview Hospital, Cleveland, OH, USA.; Meshalkin National Medical Research Center, Novosibirsk, Russia.; Department of Anesthesiology and Intensive Care Medicine, Northern State Medical University, Arkhangelsk, Russia.; SIDS Hospital & Research Centre, Surat, India.; Anesthesiology and Intensive Care Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; V. Negovskiy Reanimatology Research Institute, Moscow, Russia.; M. Vladimirskiy Moscow Regional Clinical and Research Institute, Moscow, Russia.; Department of Anaesthesia and Pain Management Santa Creu i Sant Pau University Hospital, Barcelona, Spain.; Trauma & Orthopaedic surgery department, Hospital Clínico Universitario, Valladolid, Spain.; School of Nursing, McMaster University, Hamilton, ON, Canada.; Department of Surgery, McMaster University, Hamilton, ON, Canada.; Department of Medicine, London Health Sciences Centre, London, ON, Canada.; Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.; Department of General Anaesthesiology, Emergency- and Intensive Care Medicine, Medical University Graz, Graz, Austria.; Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada.; Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.; Department of Anesthesiology, GH Paris Saint Joseph, Paris, France.

DOI: 10.1186/s13063-021-05992-1

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MeSH Terms: Antifibrinolytic Agents, Blood Loss, Surgical, Humans, Hypotension, Perioperative Care, Tranexamic Acid