Tranexamic acid and hypotension-avoidance in major non cardiac surgery

Tranexamic acid and hypotension-avoidance in major non cardiac surgery

 

POISE-3: PeriOperative ISchemic Evaluation-3 Trial

The Perioperative Ischemic Evaluation-3 (POISE-3) trial will examine the safety and efficacy of tranexamic acid and the effect of a hypotension-avoidance strategy on ischaemic and bleeding endpoints in major noncardiac surgery in 10,000 participants.

The results of the tranexamic arm was presented at the ANZCA Annual Scientfic Meeting 2022 by Dr Tom Painter.

The trial received funding from the Australian National Health and Medical Research Council in 2019 (APP1162362) for $1.2 million dollars and completed recruitment of 9561 patients globally from 149 centres sites by mid 2021. The Australian and New Zealand sites which were supported by the NHMRC grant recruited 743 patients from 20 centres.
For all the latest updates on POISE-3, follow @POISE3_ANZ on Twitter.

Principal investigators

Professor Kate Leslie AO and Dr Thomas Painter (Australian arm).
The trial has been developed and is being run internationally by the Population Health Research Institute in Canada and led by Dr PJ Devereaux.

Recruitment

From 2018 to 2021, the study recruited 9561 patients across 149 sites in 24 countries. The ANZCA CTN made an outstanding contribution to the trial with a total of 743 patients recruited across 20 centres between April 2019 and July 2021.

Participating countries

Australia, New Zealand, Canada and 19 others.

Trial summary

POISE-3 is a multicentre, international, randomised controlled trial of tranexamic acid (TXA) versus placebo and, using a partial factorial, of a perioperative hypotension avoidance versus hypertension-avoidance strategy in adults undergoing non cardiac surgery.

Sample Size
10000 patients

Study Duration
Five years

Primary outcomes
The co-primary efficacy outcome for the TXA trial is a composite of life-threatening bleeding, major bleeding, and critical organ bleeding at 30 days after randomisation. The co-primary safety outcome for the TXA trial is a composite of myocardial injury after noncardiac surgery (MINS), non-haemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism at 30 days after randomisation. The primary outcome for the blood pressure management trial is a composite of vascular death, and non-fatal MINS, stroke, and cardiac arrest 30 days after randomisation.

Tranexamic acid arm results

The POISE-3 study randomised patients having noncardiac surgery to tranexamic acid (TXA) or placebo. The incidence of bleeding outcome was significantly lower with TXA (9.1%) than with placebo (11.7%) (hazard ratio, 0.76; 95% CI, 0.67 to 0.87). The incidence of the safety outcome (myocardial injury, stroke, arterial thrombosis, VTE) was 14.2% in the TXA group and 13.9% in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14) but non-inferiority was not established. As the absolute difference in the safety outcome was small, wider use of TXA in noncardiac surgery seems justified. As TXA is inexpensive these results will be rapidly translated into practice in Australia.

Publications

Devereaux PJ, Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Martínez-Zapata MJ, Wang CY, Xavier D, Ofori SN, Wang MK, Efremov S, Landoni G, Kleinlugtenbelt YV, Szczeklik W, Schmartz D, Garg AX, Short TG, Wittmann M, Meyhoff CS, Amir M, Torres D, Patel A, Duceppe E, Ruetzler K, Parlow JL, Tandon V, Fleischmann E, Polanczyk CA, Lamy A, Astrakov SV, Rao M, Wu WKK, Bhatt K, de Nadal M, Likhvantsev VV, Paniagua P, Aguado HJ, Whitlock RP, McGillion MH, Prystajecky M, Vincent J, Eikelboom J, Copland I, Balasubramanian K, Turan A, Bangdiwala SI, Stillo D, Gross PL, Cafaro T, Alfonsi P, Roshanov PS, Belley-Côté EP, Spence J, Richards T, VanHelder T, McIntyre W, Guyatt G, Yusuf S, Leslie K; POISE-3 Investigators. Tranexamic Acid in Patients Undergoing Noncardiac Surgery. N Engl J Med. 2022 Apr 2. doi: 10.1056/NEJMoa2201171. Epub ahead of print. PMID: 35363452.

 

Marcucci M, Painter TW, Conen D, Leslie K, Lomivorotov VV, Sessler D, Chan MTV, Borges FK, Martínez Zapata MJ, Wang CY, Xavier D, Ofori SN, Landoni G, Efremov S, Kleinlugtenbelt YV, Szczeklik W, Schmartz D, Garg AX, Short TG, Wittmann M, Meyhoff CS, Amir M, Torres D, Patel A, Duceppe E, Ruetzler K, Parlow JL, Tandon V, Wang MK, Fleischmann E, Polanczyk CA, Jayaram R, Astrakov SV, Rao M, VanHelder T, Wu WKK, Cheong CC, Ayad S, Abubakirov M, Kirov M, Bhatt K, de Nadal M, Likhvantsev V, Iglesisas PP, Aguado HJ, McGillion M, Lamy A, Whitlock RP, Roshanov P, Stillo D, Copland I, Vincent J, Balasubramanian K, Bangdiwala SI, Biccard B, Kurz A, Srinathan S, Petit S, Eikelboom J, Richards T, Gross PL, Alfonsi P, Guyatt G, Belley-Cote E, Spence J, McIntyre W, Yusuf S, Devereaux PJ. 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. 2022 Jan 31;23(1):101. doi: 10.1186/s13063-021-05992-1. PMID: 35101083; PMCID: PMC8805242.

Funding

Canadian Institutes of Health Research and others.

The Australian and New Zealand arm was supported by the Australian National Health and Medical Research Council. 

Trial registration

ClinicalTrials.gov number, NCT03505723

Participating hospitals

Australian hospitals
Austin Health
Box Hill Hospital
Dandenong Hospital
Fiona Stanley Hospital
Flinders Medical Centre
Goulburn Valley Health
John Hunter Hospital
Peter Mac Hospital
Prince of Wales Hospital
Princess Alexandra Hsopital
Queen Elizabeth II Jubilee Hospital
Royal Adelaide Hospital
Royal Hobart Hospital
Royal Melbourne Hospital
Royal Perth Hospital
Western Health Sunshine, Williamstown and Footscray Hospitals
Westmead Hospital
New Zealand hospitals 
Auckland City Hsopital
Middlemore and Manukau Hospital
Waikato Hospital

Media Release

For more information

For further information about this study, please contact the POISE-3 Project Manager, Gillian Ormond by email.

Last updated 10:45 14.11.2024