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
Authors: Marcucci Maura , Painter Thomas W. , Conen David , Leslie Kate , Lomivorotov Vladimir V. , Sessler Daniel , Chan Matthew T. V. , Borges Flavia K. , Martínez Zapata Maria J. , Wang C. Y. , Xavier Denis , Ofori Sandra N. , Landoni Giovanni , Efremov Sergey , Kleinlugtenbelt Ydo V. , Szczeklik Wojciech , Schmartz Denis , Garg Amit X. , Short Timothy G. , Wittmann Maria , Meyhoff Christian S. , Amir Mohammed , Torres David , Patel Ameen , Duceppe Emmanuelle , Ruetzler Kurtz , Parlow Joel L. , Tandon Vikas , Wang Michael K. , Fleischmann Edith , Polanczyk Carisi A. , Jayaram Raja , Astrakov Sergey V. , Rao Mangala , VanHelder Tomas , Wu William K. K. , Cheong Chao Chia , Ayad Sabry , Abubakirov Marat , Kirov Mikhail , Bhatt Keyur , de Nadal Miriam , Likhvantsev Valery , Iglesisas Pilar Paniagua , Aguado Hector J. , McGillion Michael , Lamy Andre , Whitlock Richard P. , Roshanov Pavel , Stillo David , Copland Ingrid , Vincent Jessica , Balasubramanian Kumar , Bangdiwala Shrikant I. , Biccard Bruce , Kurz Andrea , Srinathan Sadeesh , Petit Shirley , Eikelboom John , Richards Toby , Gross Peter L. , Alfonsi Pascal , Guyatt Gordon , Belley-Cote Emily , Spence Jessica , McIntyre William , Yusuf Salim , Devereaux P. J. 
Published: January 2022

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.