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.

Antifibrinolytic Agents / adverse effects Blood Loss, Surgical / prevention & control Humans Hypotension / chemically induced Perioperative Care Tranexamic Acid / adverse effects
Cardiovascular complications Noncardiac surgery Perioperative bleeding Perioperative hypotension Randomized controlled trial Tranexamic acid

Journal

Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253

Informations de publication

Date de publication:
31 Jan 2022
Historique:
received: 24 09 2021
accepted: 29 12 2021
entrez: 1 2 2022
pubmed: 2 2 2022
medline: 3 2 2022
Statut: epublish

Résumé

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. 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. 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. ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Sections du résumé

BACKGROUND 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 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 CONCLUSIONS
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 BACKGROUND
ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Identifiants

DOI: 10.1186/s13063-021-05992-1 PMID: 35101083 PMC: PMC8805242
pubmed: 35101083
doi: 10.1186/s13063-021-05992-1
pii: 10.1186/s13063-021-05992-1
pmc: PMC8805242
doi:

Substances chimiques

Antifibrinolytic Agents 0
Tranexamic Acid 6T84R30KC1

Banques de données

ClinicalTrials.gov
['NCT03505723']

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

101

Subventions

Organisme : CIHR
ID : FDN-143302
Pays : Canada
Organisme : Research Grant Council, Hong Kong SAR
ID : 14104419
Organisme : National Health and Medical Research Council, Australia
ID : 1162362

Informations de copyright

© 2022. The Author(s).

Références

JAMA. 2017 Oct 10;318(14):1346-1357
pubmed: 28973220
Lancet. 2010 Jul 3;376(9734):23-32
pubmed: 20554319
Anesthesiology. 1994 Aug;81(2):299-307
pubmed: 8053578
Anesth Analg. 2018 Jun;126(6):1936-1945
pubmed: 29077608
J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264
pubmed: 30153967
Knee Surg Sports Traumatol Arthrosc. 2012 Sep;20(9):1742-52
pubmed: 22065294
Pilot Feasibility Stud. 2020 Jul 21;6:104
pubmed: 32699643
Circulation. 2012 Jul 10;126(2):207-12
pubmed: 22679143
BMJ. 2012 May 17;344:e3054
pubmed: 22611164
Ann Intern Med. 2011 Apr 19;154(8):523-8
pubmed: 21502650
Anesthesiology. 2017 Jan;126(1):16-27
pubmed: 27775997
Lancet. 2020 Jun 20;395(10241):1927-1936
pubmed: 32563378
J Bone Joint Surg Br. 2011 Jan;93(1):39-46
pubmed: 21196541
JAMA. 2014 Dec 3;312(21):2254-64
pubmed: 25399007
Anesthesiology. 2017 Jan;126(1):47-65
pubmed: 27792044
CMAJ. 2019 Jul 29;191(30):E830-E837
pubmed: 31358597
Lancet. 2017 May 27;389(10084):2105-2116
pubmed: 28456509
Thromb Res. 2009 Mar;123(5):687-96
pubmed: 19007970
Ann Surg. 1990 Nov;212(5):567-80
pubmed: 2241312
BJS Open. 2021 Mar 5;5(2):
pubmed: 33839754
Br J Anaesth. 2017 Jul 1;119(1):174
pubmed: 28974084
N Engl J Med. 2017 Jan 12;376(2):136-148
pubmed: 27774838
Anesth Analg. 2002 Aug;95(2):273-7, table of contents
pubmed: 12145033
Eur J Orthop Surg Traumatol. 2015 Apr;25(3):525-41
pubmed: 25430635
JAMA. 2012 Dec 26;308(24):2594-604
pubmed: 23268518
Eur Spine J. 2013 Sep;22(9):1950-7
pubmed: 23657623
J Clin Anesth. 2017 Dec;43:77-83
pubmed: 29055803
JAMA Surg. 2021 Apr 14;:e210884
pubmed: 33851983
N Engl J Med. 2014 Apr 17;370(16):1494-503
pubmed: 24679062
Anesthesiology. 2013 Sep;119(3):507-15
pubmed: 23835589
BMJ. 2010 Mar 30;340:c117
pubmed: 20354011
JAMA. 2017 Apr 25;317(16):1642-1651
pubmed: 28444280
Anesthesiology. 2015 Jul;123(1):79-91
pubmed: 25929547
Anaesthesia. 1997 Feb;52(2):107-11
pubmed: 9059090
Anesth Analg. 2001 Jan;92(1):26-30
pubmed: 11133595
CMAJ. 2020 Aug 10;192(32):E901-E906
pubmed: 32778601
Lancet. 2008 May 31;371(9627):1839-47
pubmed: 18479744
Br J Anaesth. 2021 Jan;126(1):163-171
pubmed: 32768179
N Engl J Med. 2014 Apr 17;370(16):1504-13
pubmed: 24679061
Anaesthesist. 2007 Jun;56(6):557-61
pubmed: 17435976
JAMA. 2012 Jun 6;307(21):2295-304
pubmed: 22706835

Auteurs

Maura Marcucci (M)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. marcum2@mcmaster.ca.
Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. marcum2@mcmaster.ca.
Population Health Research Institute, Hamilton, ON, Canada. marcum2@mcmaster.ca.
ORCID: 0000-0002-8468-7991

Thomas W Painter (TW)

Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Department of Anaesthesia, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

David Conen (D)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Kate Leslie (K)

Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Australia.
Department of Critical Care Medicine, Melbourne Medical School, University of Melbourne, Melbourne, Australia.

Vladimir V Lomivorotov (VV)

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.

Daniel Sessler (D)

Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Matthew T V Chan (MTV)

The Chinese University of Hong Kong, Hong Kong, China.

Flavia K Borges (FK)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Maria J Martínez Zapata (MJ)

Iberoamerican Cochrane Centre-Public Health and Clinical Epidemiology Service, IIB Sant Pau, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

C Y Wang (CY)

Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Denis Xavier (D)

St. John's Medical College, Bangalore, India.

Sandra N Ofori (SN)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Giovanni Landoni (G)

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

Sergey Efremov (S)

Saint Petersburg State University Hospital, Saint Petersburg, Russia.

Ydo V Kleinlugtenbelt (YV)

Department of Orthopedic and Trauma Surgery, Deventer Ziekenhuis, Deventer, the Netherlands.

Wojciech Szczeklik (W)

Jagiellonian University Medical College, Center for Intensive Care and Perioperative Medicine, Krakow, Poland.

Denis Schmartz (D)

CHU Brugmann, Université libre de Bruxelles, Brussels, Belgium.

Amit X Garg (AX)

Population Health Research Institute, Hamilton, ON, Canada.
Department of Medicine, Epidemiology and Biostatistics, Western University, London, ON, Canada.

Timothy G Short (TG)

Auckland City Hospital, Auckland, New Zealand.
University of Auckland, School of Health Sciences, Auckland, New Zealand.

Maria Wittmann (M)

Department of Anesthesiology, University Hospital, Bonn, Germany.

Christian S Meyhoff (CS)

Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

Mohammed Amir (M)

Shifa International Hospital (STMU), Islamabad, Pakistan.

David Torres (D)

Clinica Santa Maria, Santiago, Chile.
Universidad de Los Andes, Santiago, Chile.

Ameen Patel (A)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.

Emmanuelle Duceppe (E)

Population Health Research Institute, Hamilton, ON, Canada.
Department of Medicine, Universite de Montreal, Montreal, QC, Canada.

Kurtz Ruetzler (K)

Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Joel L Parlow (JL)

Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital and Queen's University, Kingston, ON, Canada.

Vikas Tandon (V)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.

Michael K Wang (MK)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Edith Fleischmann (E)

Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.

Carisi A Polanczyk (CA)

Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Cardiology Department, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

Raja Jayaram (R)

Nuffield Department of Anaesthetics, Clinical Neurosciences, University of Oxford, Oxford, UK.

Sergey V Astrakov (SV)

City hospital No. 25, Novosibirsk, Russia.
Department of Anesthesiology, Novosibirsk State University, Novosibirsk, Russia.

Mangala Rao (M)

St. John's Medical College, Bangalore, India.

Tomas VanHelder (T)

Department of Anesthesia, McMaster University, Hamilton, ON, Canada.

William K K Wu (WKK)

The Chinese University of Hong Kong, Hong Kong, China.

Chao Chia Cheong (CC)

Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Sabry Ayad (S)

Case Western Reserve University, Anesthesiology Institute, Cleveland Clinic - Fairview Hospital, Cleveland, OH, USA.

Marat Abubakirov (M)

Meshalkin National Medical Research Center, Novosibirsk, Russia.

Mikhail Kirov (M)

Department of Anesthesiology and Intensive Care Medicine, Northern State Medical University, Arkhangelsk, Russia.

Keyur Bhatt (K)

SIDS Hospital & Research Centre, Surat, India.

Miriam de Nadal (M)

Anesthesiology and Intensive Care Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Valery Likhvantsev (V)

V. Negovskiy Reanimatology Research Institute, Moscow, Russia.
M. Vladimirskiy Moscow Regional Clinical and Research Institute, Moscow, Russia.

Pilar Paniagua Iglesisas (PP)

Department of Anaesthesia and Pain Management Santa Creu i Sant Pau University Hospital, Barcelona, Spain.

Hector J Aguado (HJ)

Trauma & Orthopaedic surgery department, Hospital Clínico Universitario, Valladolid, Spain.

Michael McGillion (M)

Population Health Research Institute, Hamilton, ON, Canada.
School of Nursing, McMaster University, Hamilton, ON, Canada.

Andre Lamy (A)

Population Health Research Institute, Hamilton, ON, Canada.
Department of Surgery, McMaster University, Hamilton, ON, Canada.

Richard P Whitlock (RP)

Population Health Research Institute, Hamilton, ON, Canada.
Department of Surgery, McMaster University, Hamilton, ON, Canada.

Pavel Roshanov (P)

Department of Medicine, London Health Sciences Centre, London, ON, Canada.

David Stillo (D)

Population Health Research Institute, Hamilton, ON, Canada.

Ingrid Copland (I)

Population Health Research Institute, Hamilton, ON, Canada.

Jessica Vincent (J)

Population Health Research Institute, Hamilton, ON, Canada.

Kumar Balasubramanian (K)

Population Health Research Institute, Hamilton, ON, Canada.

Shrikant I Bangdiwala (SI)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Bruce Biccard (B)

Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.

Andrea Kurz (A)

Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of General Anaesthesiology, Emergency- and Intensive Care Medicine, Medical University Graz, Graz, Austria.

Sadeesh Srinathan (S)

Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada.

Shirley Petit (S)

Population Health Research Institute, Hamilton, ON, Canada.

John Eikelboom (J)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Toby Richards (T)

Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.

Peter L Gross (PL)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.

Pascal Alfonsi (P)

Department of Anesthesiology, GH Paris Saint Joseph, Paris, France.

Gordon Guyatt (G)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.

Emily Belley-Cote (E)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Jessica Spence (J)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.
Department of Anesthesia, McMaster University, Hamilton, ON, Canada.

William McIntyre (W)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Salim Yusuf (S)

Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

P J Devereaux (PJ)

Department of Health Research Methods, Evidence, and Impact, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Department of Medicine, McMaster University, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada.
Population Health Research Institute, Hamilton, ON, Canada.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents hématologiques › Coagulants › Hémostatiques › Antifibrinolytiques › Rationale and design of the PeriOperative...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Complications peropératoires › Perte sanguine peropératoire › Rationale and design of the PeriOperative...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Rationale and design of the PeriOperative...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Hypotension artérielle › Rationale and design of the PeriOperative...
questionsmedicales.fr › Établissements, main d'oeuvre et services de soins de santé › Services de santé › Soins aux patients › Soins périopératoires › Rationale and design of the PeriOperative...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides carbocycliques › Acide tranéxamique › Rationale and design of the PeriOperative...