Perioperative BleedingPhase 3POISE-3NCT03505723
PeriOperative ISchemic Evaluation-3 Trial
A Phase 3 study testing Tranexamic Acid, Perioperative hypotension-avoidance strategy and Perioperative hypertension-avoidance strategy in people with Perioperative Bleeding and Venous Thrombosis, run by Population Health Research Institute at 114 sites in 23 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Perioperative Bleeding, Venous Thrombosis, Arterial Thrombosis
- What is being tested?
- Tranexamic Acid, Perioperative hypotension-avoidance strategy and Perioperative hypertension-avoidance strategy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9,535 participants
- Where
- 114 sitesin 23 countries
- Study dates
- 27 Jun 2018to 3 Feb 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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):
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
114 sites in 23 countries.
114 sites in 23 countries
Australia17 sites
Royal Adelaide Hospital
Adelaide, South Australia
Flinders Medical Centre
Bedford Park, South Australia
Eastern Health (Box Hill Hospital)
Box Hill, Victoria
Queen Elizabeth II Jubilee Hospital
Brisbane, Queensland, 4108
Dandenong Hospital
Dandenong, Victoria
Western Health
Footscray
Austin Hospital
Heidelberg, Victoria
Royal Hobart Hospital
Hobart, Tasmania
Peter MacCallum Hospital
Melbourne
Fiona Stanley Hospital
Murdoch, Western Australia
John Hunter Hospital
New Lambton
Royal Melbourne Hospital
Parkville, Victoria
Royal Perth
Perth
Princes of Wales Hospital
Randwick
Goulburn Valley Health
Shepparton
Westmead Hospital
Sydney
Princess Alexandra Hospital
Woolloongabba, Queensland
India13 sites
TD Medical College
Alappuzha
Bangalore Baptist Hospital
Bangalore
Sidhu Hospital Pvt. Ltd.
Dorāha, Punjab
NH Rabindranath Tagore International Inst. of Cardiac Sciences
Kolkata, West Bengal, 700099
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow
Lucknow, Uttar Pradesh
Christian Medical College, Ludhiana
Ludhiana, Punjab
Rahate Surgical Hospital
Nagpur, Maharashtra
Sengupta Hospital & Research Institute
Nagpur, Maharashtra
AMAI Charitable Trust's Ace Hospital
Pune, Maharashtra
Nanjappa Hospital
Shimoga, Karnataka
Surat Institute of Digestive Science
Surat, Gujarat
Government Medical College
Trivandrum, Kerala, 695011
Sumandeep Vidyapeeth & Dhiraj General Hospital
Vadodara, Gujurat
United States12 sites
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7010
Cleveland Clinic - Fairview
Cleveland, Ohio, 44111
Cleveland Clinic - Main Campus
Cleveland, Ohio, 44195
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
MD Anderson Cancer Center
Houston, Texas, 77030
Cleveland Clinic - Hillcrest
Mayfield Heights, Ohio, 44124
Yale New Haven Hospital
New Haven, Connecticut, 06510
Columbia University
New York, New York, 10027
Oregon Health & Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Cleveland Clinic, Florida
Weston, Florida, 33331
Wake Forest
Winston-Salem, North Carolina, 27157
Canada12 sites
University of Calgary, O'Brien Institute for Public Health
Calgary, Alberta
University of Alberta
Edmonton, Alberta
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Juravinski Hospital & Cancer Centre
Hamilton, Ontario, L8V 1C3
Kingston Health Sciences Centre
Kingston, Ontario
Victoria Hospital
London
CHUM
Montreal, Quebec
Royal University Hospital (Saskatoon)
Saskatoon, Saskatchewan
Sherbrooke
Sherbrooke, Quebec
University Health Network (Toronto General Hospital)
Toronto, Ontario
Health Sciences Centre
Winnipeg, Manitoba
Russia7 sites
City Hospital 1 of Arkhangelsk
Arkhangelsk
V. Negovskiy Reanimatology Research Institute
Moscow, 107031
Moscow Regional Research & Clinical Institute (MONIKI)
Moscow
City Hospital N25
Novosibirsk
E. Meshalkin National Medical Research Center
Novosibirsk
Hospital of Saint-Petersburg State University
Saint Petersburg
Tyumen State Medical University
Tyumen
Spain7 sites
Hospital Clinic - Barcelona
Barcelona
Hospital de la Sta Creu i Sant Pau
Barcelona
Hospital Vall D'Hebron
Barcelona
Hospital Dr. Josep Trueta
Girona
Hospital Ramon y Cajal
Madrid
Hospital Universitario Fundacion Alcorcon
Madrid
Hospital Clínico Universitario in Valladolid
Valladolid
Malaysia6 sites
Hospital Kuala Lumpur
Kuala Lumpur
University Malaya Medical Centre
Kuala Lumpur
Sarawak General Hospital
Kuching, Sarawak
Port Dickson Hospital
Port Dickson, Negeri Sembilan
Hospital Pulau Pinang
Pulau Pinang
Sungai Buloh Hospital
Sungai Buloh
China4 sites
West China Hospital of Sichuan University
Chengdu, Sichuan
The Fourth Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang
Second Hospital of Anhui Medical University
Hefei, Anhui
Shenzhen People's Hospital
Shenzhen, Guangdong
Germany4 sites
University Hospital RWTH Aachen
Aachen
University Hospital Bonn
Bonn
Klinikum Dortmund gGmbH
Dortmund
University Hospital Düsseldorf
Düsseldorf
Italy4 sites
Ospedale Galliera di Genova
Genova
Instituto Clinico San Siro
Milan
IRCCS San Raffaele Scientific Institute
Milan
IRCCS Galeazzi Orthopedic Institute
Milan
Denmark3 sites
Bispebjerg Hospital
Copenhagen, Capital Region
Rigshospitalet, Abdominal Centre
Copenhagen
Zealand University Hospital
Køge
New Zealand3 sites
Middlemore Hospital
Auckland
Auckland General Hospital
Grafton, Auckland
Waikato District Health Board
Hamilton
Poland3 sites
Jagiellonian University Medical College
Krakow
Specialistyczny Szpital im. E. Szczeklika w Tarnowie
Tarnów
Szpital Uniwersytecki im Karola Marcinkowskiego w Zielonej Górze
Zielona Góra
South Africa3 sites
Sefako Makgatho Health Sciences University (SMU)
Ga-Rankuwa, Gauteng
Groote Schuur Hospital
Observatory, Cape Town
Steve Biko Academic Hospital - University of Pretoria
Pretoria, Gauteng
United Kingdom3 sites
Medway NHS Foundation Trust
Gillingham
Chelsea & Westminster Hospital
London
West Middlesex Hospital
London
Belgium2 sites
CHU Brugmann
Brussels
Cliniques Universitaires Saint-Luc
Brussels
Brazil2 sites
Hospital do Coracao de Pocos de Caldas
Poços de Caldas, Minas Gerais
Hospital de Clinicas de Porto Alegre
Porto Alegre
Netherlands2 sites
Deventer Ziekenhuis
Deventer, Overijssel
Erasmus University Medical Center
Rotterdam
Pakistan2 sites
Shifa International Hospitals
Islamabad, Islamabad
Aga Khan University
Karachi
About this study
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.
Read the detailed description
The POISE-3 study is a 10,000 patient, multicentre, international, non-inferiority randomized controlled trial of tranexamic acid (TXA) versus placebo and, using a partial factorial design, of a perioperative hypotension-avoidance versus hypertension-avoidance strategy. The primary objective of the study is to determine; if TXA is superior to placebo for the occurrence of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic event; and to determine the impact of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of vascular death and major vascular events in patients who are followed for 30 days after noncardiac surgery.
- Being tested
- Tranexamic Acid, Placebo (Saline), Perioperative hypotension-avoidance strategy, Perioperative hypertension-avoidance strategy
- Keywords
- Noncardiac surgery, Myocardial injury, Perioperative myocardial infarction, Tranexamic Acid, Hypotension, Hypertension
- Medical subject headings
- Venous Thrombosis, Hypotension, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic AcidDrug
Also called TXA
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.
Placebo (Saline)Drug
Also called saline
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.
Perioperative hypotension-avoidance strategyOther
Perioperative hypotension-avoidance strategy includes:
- Preoperative algorithm that only continues some antihypertensive medications in a stepwise manner for systolic BP ≥130 mm Hg before surgery,
- Intraoperative blood pressure targeting a mean arterial pressure (MAP) ≥80 mm Hg
- 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.
Perioperative hypertension-avoidance strategyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: 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). Receives: Other: Perioperative hypertension-avoidance strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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
Number of patients who have at least one of the following: vascular death, and non-fatal life-threatening, major or critical organ bleeding, myocardial injury after noncardiac surgery, stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism,
Measured: 30 days after randomization
BIMS
Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)
Measured: 30 days after randomization
MINS
Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
Measured: 30 days after randomization
MINS not fulfilling the universal definition of myocardial infarction
Number of patients who experience a myocardial injury after noncardiac surgery (MINS) not fulfilling the 3rd universal definition of myocardial infarction
Measured: 30 days after randomization
Myocardial infarction
Number of patients who experience a myocardial infarction
Measured: 30 days after randomization
For patients in the blood pressure management arm: all-cause mortality
Number of patients who die of any cause
Measured: 30 days after randomization
For patients in the blood pressure management arm: MINS
Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
Measured: 30 days after randomization
For patients in the blood pressure management arm: Myocardial infarction
Number of patients who experience a myocardial infarction
Measured: 30 days after randomization
For patients in the blood pressure management arm: MINS not fulfilling the universal definition of myocardial infarction
Number of patients who experience MINS not fulfilling the universal definition of myocardial infarction
Measured: 30 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2018
- Study start27 Jun 2018
- Primary completion8 Nov 2021
- Study completion3 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Perioperative BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9,535 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, P.J. Devereaux, Population Health Research Institute
- Investigators
- PJ Devereaux, MD, PhD, Principal investigator, Hamilton Health Sciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03505723
- Sponsor's protocol ID
- 2018.02.08
- Acronym
- POISE-3
- Status last verified
- Feb 2025
- First submitted
- 16 Mar 2018
- Last updated
- 12 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40456161Park 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.
PubMed 39813061POISE-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.
PubMed 39490985Marcucci 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.
PubMed 37094336Devereaux 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.
PubMed 35363452Marcucci 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.
PubMed 35101083
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PeriOperative ISchemic Evaluation-3 Trial
- ClinicalTrials.gov ID
- NCT03505723
- Acronym / sponsor ID
- POISE-3 / 2018.02.08
- Keywords
- Noncardiac surgery, Myocardial injury, Perioperative myocardial infarction, Tranexamic Acid, Hypotension, Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9,535 participants (actual)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Study start
- 27 Jun 2018 (actual)
- Primary completion
- 8 Nov 2021 (actual)
- Study completion
- 3 Feb 2023 (actual)
- First posted
- 23 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The POISE-3 study is a 10,000 patient, multicentre, international, non-inferiority randomized controlled trial of tranexamic acid (TXA) versus placebo and, using a partial factorial design, of a perioperative hypotension-avoidance versus hypertension-avoidance strategy. The primary objective of the study is to determine; if TXA is superior to placebo for the occurrence of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic event; and to determine the impact of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of vascular death and major vascular events in patients who are followed for 30 days after noncardiac surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Tranexamic Acid (TXA) | Active comparator | Drug: Tranexamic AcidPatients 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). |
| Placebo (0.9% normal saline) | Placebo comparator | Drug: Placebo (Saline)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). |
| Hypotension-avoidance strategy | Active comparator | Other: Perioperative hypotension-avoidance strategyAims to avoid hypotension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative). |
| Perioperative hypertension-avoidance strategy | Placebo comparator | Other: Perioperative hypertension-avoidance strategyAims to avoid hypertension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative). |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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):
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic AcidAlso: TXAWithin 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. | Drug | Tranexamic Acid (TXA) |
| Placebo (Saline)Also: salineWithin 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. | Drug | Placebo (0.9% normal saline) |
| Perioperative hypotension-avoidance strategyPerioperative 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. | Other | Hypotension-avoidance strategy |
| Perioperative hypertension-avoidance strategyPerioperative 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. | Other | Perioperative hypertension-avoidance strategy |
Primary outcome
A composite of life-threatening bleeding, major bleeding, and critical organ bleeding
Time frame: 30 days after randomization
Number of patients who have at least one of the following: life-threatening bleeding, major bleeding, and critical organ bleeding
A composite of MINS, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism.
Time frame: 30 days after randomization
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.
For patients in the blood pressure management arm: A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest.
Time frame: 30 days after randomization
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.
9 secondary outcomes
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
Time frame: 30 days after randomization
BIMS
Time frame: 30 days after randomization
MINS
Time frame: 30 days after randomization
MINS not fulfilling the universal definition of myocardial infarction
Time frame: 30 days after randomization
Myocardial infarction
Time frame: 30 days after randomization
For patients in the blood pressure management arm: all-cause mortality
Time frame: 30 days after randomization
For patients in the blood pressure management arm: MINS
Time frame: 30 days after randomization
For patients in the blood pressure management arm: Myocardial infarction
Time frame: 30 days after randomization
For patients in the blood pressure management arm: MINS not fulfilling the universal definition of myocardial infarction
Time frame: 30 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Derived from this study: PubMed 40456161Marcucci 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.
- Derived from this study: PubMed 39813061Park 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.
- Derived from this study: PubMed 39490985POISE-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.
- Derived from this study: PubMed 37094336Marcucci 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.
- Derived from this study: PubMed 35363452Devereaux 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.
- Derived from this study: PubMed 35101083Marcucci 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
PJ Devereaux, MD, PhD principal investigator
Hamilton Health Sciences Corporation
114 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic Acid, Perioperative hypotension-avoidance strategy and Perioperative hypertension-avoidance strategy in people with Perioperative Bleeding and Venous Thrombosis, run by Population Health Research Institute at 114 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 114 sites in Australia, India, United States, Canada, Russia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite of life-threatening bleeding, major bleeding, and critical organ bleeding (time frame: 30 days after randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03505723, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2025.