PeriOperative ISchemic Evaluation-3 Trial

NCT03505723 | Completed Phase 3 DMC

• 1 other identifier: 2018.02.08
• Study Type: interventional
• Target: 9,535
• Locations: 22 countries
• Sites: 113

Brief Summary

This study is a multicentre, international, randomized controlled trial of tranexamic acid (TXA) versus placebo and, using a partial factorial design, of a perioperative hypotension-avoidance versus hypertension-avoidance strategy.

Conditions

Perioperative Bleeding; Venous Thrombosis; Arterial Thrombosis

Keywords

Noncardiac surgery; Myocardial injury; Perioperative myocardial infarction; Tranexamic Acid; Hypotension; Hypertension

Outcome Measures

Primary Outcomes (3)

• A composite of life-threatening bleeding, major bleeding, and critical organ bleeding

  Number of patients who have at least one of the following: life-threatening bleeding, major bleeding, and critical organ bleeding

  30 days after randomization

• A composite of MINS, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism.

  Number of patients who have at least one of the following: myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism.

  30 days after randomization

• For patients in the blood pressure management arm: A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest.

  Number of patients enrolled in the blood pressure management arm who have at least one of the following: vascular death, non-fatal myocardial injury after noncardiac surgery, non-fatal stroke, and non-fatal cardiac arrest.

  30 days after randomization

Secondary Outcomes (9)

• A net risk-benefit outcome as a composite of vascular death, and non-fatal life-threatening,major or critical organ bleeding,MINS,stroke,peripheral arterial thrombosis,and symptomatic proximal venous thromboembolism

  30 days after randomization

• BIMS

  30 days after randomization

• MINS

  30 days after randomization

• MINS not fulfilling the universal definition of myocardial infarction

  30 days after randomization

• Myocardial infarction

  30 days after randomization

Other Outcomes (68)

• Life threatening bleeding

  30 days after randomization

• Major bleeding

  30 days after randomization

• Critical organ bleeding

  30 days after randomization

Study Arms (4)

Tranexamic Acid (TXA)

ACTIVE COMPARATOR

Patients will receive a 1g loading dose of intravenous TXA before surgery and a 1g loading dose of intravenous TXA at the end of surgery (wound closure).

Drug: Tranexamic Acid

Placebo (0.9% normal saline)

PLACEBO COMPARATOR

Patients will receive a 1g loading dose of placebo (0.9% normal saline) before surgery and a 1g loading dose of placebo (0.9% normal saline) at the end of surgery (wound closure).

Drug: Placebo (Saline)

Hypotension-avoidance strategy

ACTIVE COMPARATOR

Aims to avoid hypotension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative).

Other: Perioperative hypotension-avoidance strategy

Perioperative hypertension-avoidance strategy

PLACEBO COMPARATOR

Aims to avoid hypertension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative).

Other: Perioperative hypertension-avoidance strategy

Interventions

Tranexamic Acid DRUG

Within 20 minutes preceding the anticipated skin incision, patients will receive intravenous TXA at a loading dose of 1g over 10 minutes, with a second 1g bolus given at the end of surgery when closing the wound.

Also known as: TXA

Tranexamic Acid (TXA)

Placebo (Saline) DRUG

Within 20 minutes preceding the anticipated skin incision, patients will receive intravenous placebo (0.9% normal saline) at a loading dose of 1g over 10 minutes, with a second 1g bolus given at the end of surgery when closing the wound.

Also known as: saline

Placebo (0.9% normal saline)

Perioperative hypotension-avoidance strategy OTHER

Perioperative hypotension-avoidance strategy includes: 1. Preoperative algorithm that only continues some antihypertensive medications in a stepwise manner for systolic BP ≥130 mm Hg before surgery, 2. Intraoperative blood pressure targeting a mean arterial pressure (MAP) ≥80 mm Hg 3. Postoperative algorithm that only continues some antihypertensive medications in a stepwise manner for systolic BP ≥130 mm Hg during the first 48 hours after surgery.

Hypotension-avoidance strategy

Perioperative hypertension-avoidance strategy OTHER

Perioperative hypertension-avoidance strategy (i.e., routine care) continues all antihypertensive drugs before and after surgery and an intraoperative BP strategy targeting a MAP ≥60 mm Hg.

Perioperative hypertension-avoidance strategy

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergoing noncardiac surgery;
• ≥ 45 years of age;
• Expected to require at least an overnight hospital admission after surgery;
• Provide written informed consent to participate in the POISE-3 Trial, AND
• Fulfill ≥1 of the following 6 criteria (A-F):
• A. NT-proBNP ≥200 ng/L B. History of coronary artery disease C. History of peripheral arterial disease D. History of stroke E. Undergoing major vascular surgery; OR F. Any 3 of 9 risk criteria i. Undergoing major surgery; ii. History of congestive heart failure; iii. History of a transient ischemic attack; iv. Diabetes and currently taking an oral hypoglycemic agent or insulin; v. Age \>70 years; vi. History of hypertension; vii. Serum creatinine \> 175 µmol/L (\> 2.0 mg/dl); viii. History of smoking within 2 years of surgery; ix. Undergoing emergent/urgent surgery.

You may not qualify if:

• Patients undergoing cardiac surgery
• Patients undergoing cranial neurosurgery
• Planned use of systemic TXA during surgery
• Low-risk surgical procedure (based on individual physician's judgment)
• Hypersensitivity or known allergy to TXA
• Creatinine clearance \<30 mL/min (Cockcroft-Gault equation) or on chronic dialysis
• History of seizure disorder
• Patients with recent stroke, myocardial infarction, acute arterial thrombosis or venous thromboembolism (\<3 month)
• Patients with fibrinolytic conditions following consumption coagulopathy
• Patients with subarachnoid hemorrhage within the past 30 days
• Women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding
• Previously enrolled in POISE-3 Trial

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (114)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Cleveland Clinic, Florida

Weston, Florida, 33331, United States

Location

Columbia University

New York, New York, 10027, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7010, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic - Fairview

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic - Main Campus

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Cleveland Clinic - Hillcrest

Mayfield Heights, Ohio, 44124, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Queen Elizabeth II Jubilee Hospital

Brisbane, Queensland, 4108, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, Australia

Location

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, Australia

Location

Dandenong Hospital

Dandenong, Victoria, Australia

Location

Austin Hospital

Heidelberg, Victoria, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Location

Western Health

Footscray, Australia

Location

Peter MacCallum Hospital

Melbourne, Australia

Location

John Hunter Hospital

New Lambton, Australia

Location

Royal Perth

Perth, Australia

Location

Princes of Wales Hospital

Randwick, Australia

Location

Goulburn Valley Health

Shepparton, Australia

Location

Westmead Hospital

Sydney, Australia

Location

Medical University of Vienna

Vienna, Austria

Location

CHU Brugmann

Brussels, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Hospital do Coracao de Pocos de Caldas

Poços de Caldas, Minas Gerais, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Brazil

Location

University of Calgary, O'Brien Institute for Public Health

Calgary, Alberta, Canada

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Health Sciences Centre

Winnipeg, Manitoba, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Juravinski Hospital & Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Location

University Health Network (Toronto General Hospital)

Toronto, Ontario, Canada

Location

CHUM

Montreal, Quebec, Canada

Location

Sherbrooke

Sherbrooke, Quebec, Canada

Location

Royal University Hospital (Saskatoon)

Saskatoon, Saskatchewan, Canada

Location

Victoria Hospital

London, Canada

Location

Clinica Santa Maria

Santiago, Chile

Location

Hospital Hernan Henriquez

Temuco, Chile

Location

Second Hospital of Anhui Medical University

Hefei, Anhui, China

Location

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Location

The Fourth Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Bispebjerg Hospital

Copenhagen, Capital Region, Denmark

Location

Rigshospitalet, Abdominal Centre

Copenhagen, Denmark

Location

Zealand University Hospital

Køge, Denmark

Location

Groupe Hospitalier Paris Saint Joseph

Paris, France

Location

University Hospital RWTH Aachen

Aachen, Germany

Location

University Hospital Bonn

Bonn, Germany

Location

Klinikum Dortmund gGmbH

Dortmund, Germany

Location

University Hospital Düsseldorf

Düsseldorf, Germany

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Surat Institute of Digestive Science

Surat, Gujarat, India

Location

Sumandeep Vidyapeeth & Dhiraj General Hospital

Vadodara, Gujurat, India

Location

Nanjappa Hospital

Shimoga, Karnataka, India

Location

Government Medical College

Trivandrum, Kerala, 695011, India

Location

Rahate Surgical Hospital

Nagpur, Maharashtra, India

Location

Sengupta Hospital & Research Institute

Nagpur, Maharashtra, India

Location

AMAI Charitable Trust's Ace Hospital

Pune, Maharashtra, India

Location

Sidhu Hospital Pvt. Ltd.

Dorāha, Punjab, India

Location

Christian Medical College, Ludhiana

Ludhiana, Punjab, India

Location

Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow

Lucknow, Uttar Pradesh, India

Location

NH Rabindranath Tagore International Inst. of Cardiac Sciences

Kolkata, West Bengal, 700099, India

Location

TD Medical College

Alappuzha, India

Location

Bangalore Baptist Hospital

Bangalore, India

Location

Ospedale Galliera di Genova

Genova, Italy

Location

Instituto Clinico San Siro

Milan, Italy

Location

IRCCS San Raffaele Scientific Institute

Milan, Italy

Location

IRCCS Galeazzi Orthopedic Institute

Milan, Italy

Location

Port Dickson Hospital

Port Dickson, Negeri Sembilan, Malaysia

Location

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, Malaysia

Location

Sungai Buloh Hospital

Sungai Buloh, Malaysia

Location

Deventer Ziekenhuis

Deventer, Overijssel, Netherlands

Location

Erasmus University Medical Center

Rotterdam, Netherlands

Location

Auckland General Hospital

Grafton, Auckland, New Zealand

Location

Middlemore Hospital

Auckland, New Zealand

Location

Waikato District Health Board

Hamilton, New Zealand

Location

Shifa International Hospitals

Islamabad, Islamabad, Pakistan

Location

Aga Khan University

Karachi, Pakistan

Location

Jagiellonian University Medical College

Krakow, Poland

Location

Specialistyczny Szpital im. E. Szczeklika w Tarnowie

Tarnów, Poland

Location

Szpital Uniwersytecki im Karola Marcinkowskiego w Zielonej Górze

Zielona Góra, Poland

Location

City Hospital 1 of Arkhangelsk

Arkhangelsk, Russia

Location

V. Negovskiy Reanimatology Research Institute

Moscow, 107031, Russia

Location

Moscow Regional Research & Clinical Institute (MONIKI)

Moscow, Russia

Location

City Hospital N25

Novosibirsk, Russia

Location

E. Meshalkin National Medical Research Center

Novosibirsk, Russia

Location

Hospital of Saint-Petersburg State University

Saint Petersburg, Russia

Location

Tyumen State Medical University

Tyumen, Russia

Location

Groote Schuur Hospital

Observatory, Cape Town, South Africa

Location

Sefako Makgatho Health Sciences University (SMU)

Ga-Rankuwa, Gauteng, South Africa

Location

Steve Biko Academic Hospital - University of Pretoria

Pretoria, Gauteng, South Africa

Location

Hospital Clinic - Barcelona

Barcelona, Spain

Location

Hospital de la Sta Creu i Sant Pau

Barcelona, Spain

Location

Hospital Vall D'Hebron

Barcelona, Spain

Location

Hospital Dr. Josep Trueta

Girona, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario Fundacion Alcorcon

Madrid, Spain

Location

Hospital Clínico Universitario in Valladolid

Valladolid, Spain

Location

Medway NHS Foundation Trust

Gillingham, United Kingdom

Location

Chelsea & Westminster Hospital

London, United Kingdom

Location

West Middlesex Hospital

London, United Kingdom

Location

Related Publications (6)

• Marcucci M, Chan MTV, Painter TW, Efremov S, Aguado HJ, Astrakov SV, Kleinlugtenbelt YV, Patel A, Cata JP, Amir M, Kirov M, Leslie K, Duceppe E, Borges FK, de Nadal M, Tandon V, Landoni G, Likhvantsev VV, Lomivorotov V, Sessler DI, Martinez-Zapata MJ, Xavier D, Fleischmann E, Wang CY, Meyhoff CS, Wittmann M, Torres D, Highton D, Jacka M, B V, Zarnke K, Sidhu RS, Oriani G, Ayad S, Minear S, Weaver TE, Ruetzler K, Brusasco C, Parlow JL, Maxwell E, Miller S, Mrkobrada M, Bhatt KSC, Rahate P, Kowark A, De Blasio G, Ofori SN, Conen D, Srinathan S, Szczeklik W, Jayaram R, Ellerkmann RK, Momeni M, Copland I, Vincent J, Balasubramanian K, Li Z, Wang MK, Li D, McGillion MH, Kurz A, Sharma M, Short TG, Devereaux PJ; cogPOISE-3 Trial Investigators and Study Groups. Effects of a Hypotension-Avoidance Versus a Hypertension-Avoidance Strategy on Neurocognitive Outcomes After Noncardiac Surgery. Ann Intern Med. 2025 Jul;178(7):909-920. doi: 10.7326/ANNALS-24-02841. Epub 2025 Jun 3.

  PMID: 40456161 DERIVED

• Park LJ, Marcucci M, Ofori SN, Borges FK, Nenshi R, Kanstrup CTB, Rosen M, Landoni G, Lomivorotov V, Painter TW, Xavier D, Martinez-Zapata MJ, Szczeklik W, Meyhoff CS, Chan MTV, Simunovic M, Bogach J, Serrano PE, Balasubramanian K, Cadeddu M, Yang I, Kim WH, Devereaux PJ. Safety and Efficacy of Tranexamic Acid in General Surgery. JAMA Surg. 2025 Mar 1;160(3):267-274. doi: 10.1001/jamasurg.2024.6048.

  PMID: 39813061 DERIVED

• POISE-3 Trial Investigators and Study Groups. A sub-study of the POISE-3 randomized trial examined effects of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of acute kidney injury. Kidney Int. 2025 Jan;107(1):155-168. doi: 10.1016/j.kint.2024.10.007. Epub 2024 Oct 25.

  PMID: 39490985 DERIVED

• Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Leslie K, Duceppe E, Martinez-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, Ruetzler K, Parlow JL, Tandon V, Fleischmann E, Polanczyk CA, Lamy A, Jayaram R, Astrakov SV, Wu WKK, Cheong CC, Ayad S, Kirov M, de Nadal M, Likhvantsev VV, Paniagua P, Aguado HJ, Maheshwari K, Whitlock RP, McGillion MH, Vincent J, Copland I, Balasubramanian K, Biccard BM, Srinathan S, Ismoilov S, Pettit S, Stillo D, Kurz A, Belley-Cote EP, Spence J, McIntyre WF, Bangdiwala SI, Guyatt G, Yusuf S, Devereaux PJ; POISE-3 Trial Investigators and Study Groups. Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial. Ann Intern Med. 2023 May;176(5):605-614. doi: 10.7326/M22-3157. Epub 2023 Apr 25.

  PMID: 37094336 DERIVED

• Devereaux PJ, Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Martinez-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-Cote 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 May 26;386(21):1986-1997. doi: 10.1056/NEJMoa2201171. Epub 2022 Apr 2.

  PMID: 35363452 DERIVED

• Marcucci M, Painter TW, Conen D, Leslie K, Lomivorotov VV, Sessler D, Chan MTV, Borges FK, Martinez 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 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Hypotension; Hypertension

Interventions

Tranexamic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• PJ Devereaux, MD, PhD

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal Investigator

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: April 23, 2018
• Study Start: June 27, 2018
• Primary Completion: November 8, 2021
• Study Completion: February 3, 2023
• Last Updated: February 12, 2025

Record last verified: 2025-02

Locations

CL (2); IT (4); PL (3); AU (17); BR (2); RU (7); ZA (3); BE (2); FR (1); MY (6); US (12); ES (7); CN (4); NL (2); IN (13); CA (12); NZ (3); PA (2); GB (3); DK (3); DE (4); HK (1)