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

Trials

Miriam de Nadal¹  Timothy G. Short²  Denis Schmartz³  Sabry Ayad⁴  Sergey V. Astrakov⁵  David Torres⁶  Christian S. Meyhoff⁷  Pilar Paniagua Iglesisas⁸  Kate Leslie⁹  Bruce Biccard^1,10  Chao Chia Cheong^1,11  C. Y. Wang^1,11  Giovanni Landoni^1,12  Edith Fleischmann^1,13  Tomas VanHelder^1,14  Mikhail Kirov^1,15  Vladimir V. Lomivorotov^1,16  Joel L. Parlow^1,17  Pascal Alfonsi^1,18  Maria Wittmann^1,19  Maura Marcucci^2,20  P. J. Devereaux^2,20  Michael K. Wang^2,20  Shrikant I. Bangdiwala^2,20  Jessica Spence^2,20  Sandra N. Ofori^2,20  Flavia K. Borges^2,20  Gordon Guyatt^2,20  Pavel Roshanov^2,21  Salim Yusuf^2,22  Vikas Tandon^2,22  Ameen Patel^2,22  Emily Belley-Cote^2,22  William McIntyre^2,22  David Conen^2,22  Peter L. Gross^2,22  John Eikelboom^2,22  Ydo V. Kleinlugtenbelt^2,23  Andrea Kurz^2,24  Kurtz Ruetzler^2,24  Daniel Sessler^2,24  Sadeesh Srinathan^2,25  Thomas W. Painter^2,26  Toby Richards^2,27  Maria J. Martínez Zapata^2,28  Wojciech Szczeklik^2,29  Marat Abubakirov^3,30  Raja Jayaram^3,31  Emmanuelle Duceppe^3,32  Shirley Petit^3,32  Michael McGillion^3,32  Andre Lamy^3,32  Ingrid Copland^3,32  Jessica Vincent^3,32  Kumar Balasubramanian^3,32  David Stillo^3,32  Amit X. Garg^3,32  Richard P. Whitlock^3,32  Keyur Bhatt^3,33  Sergey Efremov^3,34  Mohammed Amir^3,35  Denis Xavier^3,36  Mangala Rao^3,36  Matthew T. V. Chan^3,37  William K. K. Wu^3,37  Hector J. Aguado^3,38  Carisi A. Polanczyk^3,39  Valery Likhvantsev^4,40 

[1] Anesthesiology and Intensive Care Department, Hospital Universitari Vall d’Hebron;Auckland City Hospital;CHU Brugmann, Université libre de Bruxelles;Case Western Reserve University, Anesthesiology Institute, Cleveland Clinic - Fairview Hospital;City hospital No. 25;Clinica Santa Maria;Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen;Department of Anaesthesia and Pain Management Santa Creu i Sant Pau University Hospital;Department of Anaesthesia and Pain Management, Royal Melbourne Hospital;Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and University of Cape Town;Department of Anaesthesiology, Faculty of Medicine, University of Malaya;Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute;Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna;Department of Anesthesia, McMaster University;Department of Anesthesiology and Intensive Care Medicine, Northern State Medical University;Department of Anesthesiology and Intensive Care, E. Meshalkin National Medical Research Center;Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital and Queen’s University;Department of Anesthesiology, GH Paris Saint Joseph;Department of Anesthesiology, University Hospital;Department of Health Research Methods, Evidence, and Impact, McMaster University;Department of Medicine, London Health Sciences Centre;Department of Medicine, McMaster University;Department of Orthopedic and Trauma Surgery, Deventer Ziekenhuis;Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic;Department of Surgery, University of Manitoba;Discipline of Acute Care Medicine, University of Adelaide;Faculty of Health and Medical Sciences, University of Western Australia;Iberoamerican Cochrane Centre-Public Health and Clinical Epidemiology Service, IIB Sant Pau, CIBER de Epidemiología y Salud Pública (CIBERESP);Jagiellonian University Medical College, Center for Intensive Care and Perioperative Medicine;Meshalkin National Medical Research Center;Nuffield Department of Anaesthetics, Clinical Neurosciences, University of Oxford;Population Health Research Institute;SIDS Hospital & Research Centre;Saint Petersburg State University Hospital;Shifa International Hospital (STMU);St. John’s Medical College;The Chinese University of Hong Kong;Trauma & Orthopaedic surgery department, Hospital Clínico Universitario;Universidade Federal do Rio Grande do Sul;V. Negovskiy Reanimatology Research Institute;

关键词: Noncardiac surgery;    Tranexamic acid;    Perioperative bleeding;    Perioperative hypotension;    Cardiovascular complications;    Randomized controlled trial;   

DOI  :  10.1186/s13063-021-05992-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown