PeriOperative ISchemic Evaluation-3 Trial

Phase 3

Completed

• Conditions: Perioperative Bleeding; Venous Thrombosis; Arterial Thrombosis
• Interventions: Drug: Placebo (Saline); Other: Perioperative hypotension-avoidance strategy; Other: Perioperative hypertension-avoidance strategy; Drug: Tranexamic Acid

• Registration Number: NCT03505723
• Lead Sponsor: Population Health Research Institute

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.

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 Timeline

• Study First Submitted: 2018-03-16
• Study First Submitted QC: 2018-04-13
• Study First Posted: 2018-04-23
• Study Start: 2018-06-27
• Primary Completion: 2021-11-08
• Study Completion: 2023-02-03
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9535

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo (0.9% normal saline)	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	Perioperative hypotension-avoidance strategy	Aims 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	Perioperative hypertension-avoidance strategy	Aims to avoid hypertension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative).
Tranexamic Acid (TXA)	Tranexamic Acid	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).

Primary Outcome Measures

Name	Time	Method
A composite of life-threatening bleeding, major bleeding, and critical organ bleeding	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.	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.	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.

Secondary Outcome Measures

Name	Time	Method
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	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,
BIMS	30 days after randomization	Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)
MINS	30 days after randomization	Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
MINS not fulfilling the universal definition of myocardial infarction	30 days after randomization	Number of patients who experience a myocardial injury after noncardiac surgery (MINS) not fulfilling the 3rd universal definition of myocardial infarction
Myocardial infarction	30 days after randomization	Number of patients who experience a myocardial infarction
For patients in the blood pressure management arm: all-cause mortality	30 days after randomization	Number of patients who die of any cause
For patients in the blood pressure management arm: MINS	30 days after randomization	Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
For patients in the blood pressure management arm: Myocardial infarction	30 days after randomization	Number of patients who experience a myocardial infarction
For patients in the blood pressure management arm: MINS not fulfilling the universal definition of myocardial infarction	30 days after randomization	Number of patients who experience MINS not fulfilling the universal definition of myocardial infarction

Trial Locations

Locations (114)

Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Hospital do Coracao de Pocos de Caldas; 🇧🇷 Poços De Caldas, Minas Gerais, Brazil

Second Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

Shenzhen People's Hospital; 🇨🇳 Shenzhen, Guangdong, China

The Fourth Affiliated Hospital of Harbin Medical University; 🇨🇳 Harbin, Heilongjiang, China

Bispebjerg Hospital; 🇩🇰 Copenhagen, Capital Region, Denmark

Zealand University Hospital; 🇩🇰 Køge, Denmark

Rigshospitalet, Abdominal Centre; 🇩🇰 Copenhagen, Denmark

Cleveland Clinic - Fairview; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic - Main Campus; 🇺🇸 Cleveland, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Cleveland Clinic, Florida; 🇺🇸 Weston, Florida, United States

Queen Elizabeth II Jubilee Hospital; 🇦🇺 Brisbane, Queensland, Australia

AMAI Charitable Trust's Ace Hospital; 🇮🇳 Pune, Maharashtra, India

Sidhu Hospital Pvt. Ltd.; 🇮🇳 Doraha, Punjab, India

TD Medical College; 🇮🇳 Alappuzha, India

Christian Medical College, Ludhiana; 🇮🇳 Ludhiana, Punjab, India

Government Medical College; 🇮🇳 Trivandrum, Kerala, India

Groupe Hospitalier Paris Saint Joseph; 🇫🇷 Paris, France

Instituto Clinico San Siro; 🇮🇹 Milan, Italy

Erasmus University Medical Center; 🇳🇱 Rotterdam, Netherlands

Medway NHS Foundation Trust; 🇬🇧 Gillingham, United Kingdom

City Hospital 1 of Arkhangelsk; 🇷🇺 Arkhangelsk, Russian Federation

Surat Institute of Digestive Science; 🇮🇳 Surat, Gujarat, India

Sengupta Hospital & Research Institute; 🇮🇳 Nagpur, Maharashtra, India

IRCCS Galeazzi Orthopedic Institute; 🇮🇹 Milano, Italy

IRCCS San Raffaele Scientific Institute; 🇮🇹 Milan, Italy

V. Negovskiy Reanimatology Research Institute; 🇷🇺 Moscow, Russian Federation

Jagiellonian University Medical College; 🇵🇱 Kraków, Poland

Hospital Ramon y Cajal; 🇪🇸 Madrid, Spain

West Middlesex Hospital; 🇬🇧 London, United Kingdom

Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada

Nanjappa Hospital; 🇮🇳 Shimoga, Karnataka, India

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

The Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Columbia University; 🇺🇸 New York, New York, United States

Wake Forest; 🇺🇸 Winston-Salem, North Carolina, United States

Cleveland Clinic - Hillcrest; 🇺🇸 Mayfield Heights, Ohio, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Eastern Health (Box Hill Hospital); 🇦🇺 Box Hill, Victoria, Australia

Austin Hospital; 🇦🇺 Heidelberg, Victoria, Australia

Dandenong Hospital; 🇦🇺 Dandenong, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Western Health; 🇦🇺 Footscray, Australia

Princes of Wales Hospital; 🇦🇺 Randwick, Australia

Peter MacCallum Hospital; 🇦🇺 Melbourne, Australia

Royal Perth; 🇦🇺 Perth, Australia

John Hunter Hospital; 🇦🇺 New Lambton, Australia

Westmead Hospital; 🇦🇺 Sydney, Australia

Goulburn Valley Health; 🇦🇺 Shepparton, Australia

Medical University of Vienna; 🇦🇹 Vienna, Austria

CHU Brugmann; 🇧🇪 Brussels, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Health Sciences Centre; 🇨🇦 Winnipeg, Manitoba, Canada

University of Calgary, O'Brien Institute for Public Health; 🇨🇦 Calgary, Alberta, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

University Health Network (Toronto General Hospital); 🇨🇦 Toronto, Ontario, Canada

Juravinski Hospital & Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

CHUM; 🇨🇦 Montreal, Quebec, Canada

Clinica Santa Maria; 🇨🇱 Santiago, Chile

Hospital Hernan Henriquez; 🇨🇱 Temuco, Chile

Victoria Hospital; 🇨🇦 London, Canada

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

University Hospital RWTH Aachen; 🇩🇪 Aachen, Germany

University Hospital Bonn; 🇩🇪 Bonn, Germany

Klinikum Dortmund gGmbH; 🇩🇪 Dortmund, Germany

University Hospital Düsseldorf; 🇩🇪 Düsseldorf, Germany

Prince of Wales Hospital; 🇭🇰 Sha Tin, Hong Kong

NH Rabindranath Tagore International Inst. of Cardiac Sciences; 🇮🇳 Kolkata, West Bengal, India

Bangalore Baptist Hospital; 🇮🇳 Bangalore, India

University Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

Ospedale Galliera di Genova; 🇮🇹 Genova, Italy

Port Dickson Hospital; 🇲🇾 Port Dickson, Negeri Sembilan, Malaysia

Hospital Kuala Lumpur; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Pulau Pinang; 🇲🇾 Pulau Pinang, Malaysia

Auckland General Hospital; 🇳🇿 Grafton, Auckland, New Zealand

Aga Khan University; 🇵🇰 Karachi, Pakistan

Middlemore Hospital; 🇳🇿 Auckland, New Zealand

Waikato District Health Board; 🇳🇿 Hamilton, New Zealand

Shifa International Hospitals; 🇵🇰 Islamabad, Islamabad Capital Territory, Pakistan

Szpital Uniwersytecki im Karola Marcinkowskiego w Zielonej Górze; 🇵🇱 Zielona Góra, Poland

City Hospital N25; 🇷🇺 Novosibirsk, Russian Federation

Moscow Regional Research & Clinical Institute (MONIKI); 🇷🇺 Moscow, Russian Federation

E. Meshalkin National Medical Research Center; 🇷🇺 Novosibirsk, Russian Federation

Tyumen State Medical University; 🇷🇺 Tyumen, Russian Federation

Sefako Makgatho Health Sciences University (SMU); 🇿🇦 Ga-Rankuwa, Gauteng, South Africa

Steve Biko Academic Hospital - University of Pretoria; 🇿🇦 Pretoria, Gauteng, South Africa

Hospital de la Sta Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Groote Schuur Hospital; 🇿🇦 Observatory, Cape Town, South Africa

Hospital of Saint-Petersburg State University; 🇷🇺 Saint Petersburg, Russian Federation

Hospital Clinic - Barcelona; 🇪🇸 Barcelona, Spain

Hospital Dr. Josep Trueta; 🇪🇸 Girona, Spain

Hospital Vall D'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Fundacion Alcorcon; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario in Valladolid; 🇪🇸 Valladolid, Spain

Chelsea & Westminster Hospital; 🇬🇧 London, United Kingdom

Specialistyczny Szpital im. E. Szczeklika w Tarnowie; 🇵🇱 Tarnów, Poland

Royal University Hospital (Saskatoon); 🇨🇦 Saskatoon, Saskatchewan, Canada

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sumandeep Vidyapeeth & Dhiraj General Hospital; 🇮🇳 Vadodara, Gujurat, India

Sungai Buloh Hospital; 🇲🇾 Sungai Buloh, Malaysia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Rahate Surgical Hospital; 🇮🇳 Nagpur, Maharashtra, India

Sarawak General Hospital; 🇲🇾 Kuching, Sarawak, Malaysia

Deventer Ziekenhuis; 🇳🇱 Deventer, Overijssel, Netherlands

Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow; 🇮🇳 Lucknow, Uttar Pradesh, India

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada