Clinical trial NCT03505723: PeriOperative ISchemic Evaluation-3 Trial
Official title: PeriOperative ISchemic Evaluation-3 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Perioperative Bleeding
Venous Thrombosis
Arterial Thrombosis
Keywords: Noncardiac surgery
Myocardial injury
Perioperative myocardial infarction
Tranexamic Acid
Hypotension
Hypertension
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2018-04-23
Enrollment: 9535
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1. Undergoing noncardiac surgery;
2. ≥ 45 years of age;
3. Expected to require at least an overnight hospital admission after surgery;
4. Provide written informed consent to participate in the POISE-3 Trial, AND
5. 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.

Exclusion criteria:

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

Primary outcomes:
measure: A composite of life-threatening bleeding, major bleeding, and critical organ bleeding
timeFrame: 30 days after randomization
measure: A composite of MINS, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism.
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest.
timeFrame: 30 days after randomization
Secondary outcomes:
measure: 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
timeFrame: 30 days after randomization
measure: BIMS
timeFrame: 30 days after randomization
measure: MINS
timeFrame: 30 days after randomization
measure: MINS not fulfilling the universal definition of myocardial infarction
timeFrame: 30 days after randomization
measure: Myocardial infarction
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: all-cause mortality
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: MINS
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: Myocardial infarction
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: MINS not fulfilling the universal definition of myocardial infarction
timeFrame: 30 days after randomization
Other outcomes:
measure: Life threatening bleeding
timeFrame: 30 days after randomization
measure: Major bleeding
timeFrame: 30 days after randomization
measure: Critical organ bleeding
timeFrame: 30 days after randomization
measure: International Society on Thrombosis and Haemostasis (ISTH) major bleeding
timeFrame: 30 days after randomization
measure: Non-hemorrhagic stroke
timeFrame: 30 days after randomization
measure: Peripheral arterial thrombosis
timeFrame: 30 days after randomization
measure: Symptomatic proximal venous thromboembolism
timeFrame: 30 days after randomization
measure: All-cause mortality
timeFrame: 30 days after randomization
measure: Vascular mortality
timeFrame: 30 days after randomization
measure: Hemorrhagic stroke
timeFrame: 30 days after randomization
measure: Transfusion rate
timeFrame: 30 days after randomization
measure: Cardiac revascularization
timeFrame: 30 days after randomization
measure: Amputation
timeFrame: 30 days after randomization
measure: Symptomatic pulmonary embolism
timeFrame: 30 days after randomization
measure: Symptomatic proximal DVT
timeFrame: 30 days after randomization
measure: Any symptomatic or asymptomatic proximal venous thromboembolism
timeFrame: 30 days after randomization
measure: Acute kidney injury
timeFrame: 30 days after randomization
measure: New renal replacement therapy
timeFrame: 30 days after randomization
measure: Re-hospitalization for vascular reasons
timeFrame: 30 days after randomization
measure: Seizures
timeFrame: 30 days after randomization
measure: Infection/sepsis
timeFrame: 30 days after randomization
measure: Disability
timeFrame: 30 days after randomization
measure: Length of hospital stay
timeFrame: 30 days after randomization
measure: Days alive and at home
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: vascular death
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: non-fatal MINS
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: non-fatal stroke
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: non-fatal cardiac arrest
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: hemorrhagic stroke
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: non-hemorrhagic stroke
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: acute kidney injury
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: new renal replacement therapy
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: acute congestive heart failure
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: new clinically important atrial fibrillation
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: sepsis
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: disability
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: cancellation/postponement of surgery on the day of surgery due to BP concerns
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: length of hospital stay
timeFrame: 30 days after randomization
measure: For patients in the blood pressure management arm: days alive and at home
timeFrame: 30 days after randomization
measure: All-cause mortality
timeFrame: 1 year after randomization
measure: Vascular mortality
timeFrame: 1 year after randomization
measure: Myocardial infarction
timeFrame: 1 year after randomization
measure: Cardiac arrest
timeFrame: 1 year after randomization
measure: Hemorrhagic stroke
timeFrame: 1 year after randomization
measure: Non-hemorrhagic stroke
timeFrame: 1 year after randomization
measure: Peripheral arterial thrombosis
timeFrame: 1 year after randomization
measure: Amputation
timeFrame: 1 year after randomization
measure: Symptomatic pulmonary embolism
timeFrame: 1 year after randomization
measure: Symptomatic proximal DVT
timeFrame: 1 year after randomization
measure: Symptomatic proximal venous thromboembolism
timeFrame: 1 year after randomization
measure: Any symptomatic or asymptomatic proximal venous thromboembolism
timeFrame: 1 year after randomization
measure: New renal replacement therapy
timeFrame: 1 year after randomization
measure: Re-hospitalization for vascular reasons
timeFrame: 1 year after randomization
measure: Seizures
timeFrame: 1 year after randomization
measure: Infection/sepsis
timeFrame: 1 year after randomization
measure: Disability
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: all-cause mortality
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: vascular mortality
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: myocardial infarction
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: cardiac arrest
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: hemorrhagic stroke
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: non-hemorrhagic stroke
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: new renal replacement therapy
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: acute congestive heart failure
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: sepsis
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm: Disability
timeFrame: 1 year after randomization
measure: For patients in the blood pressure management arm (CogPOISE-3 Sub study): Delirium
timeFrame: Post operative day one to three
measure: For patients in the blood pressure management arm (CogPOISE-3 Sub study): Cognitive decline
timeFrame: 1 year after randomization
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Weston
country: United States
facility: Cleveland Clinic, Florida
state: Florida
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Fairview
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Main Campus
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Mayfield Heights
country: United States
facility: Cleveland Clinic - Hillcrest
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Brisbane
country: Australia
facility: Queen Elizabeth II Jubilee Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Eastern Health (Box Hill Hospital)
state: Victoria
city: Dandenong
country: Australia
facility: Dandenong Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Footscray
country: Australia
facility: Western Health
city: Melbourne
country: Australia
facility: Peter MacCallum Hospital
city: New Lambton
country: Australia
facility: John Hunter Hospital
city: Perth
country: Australia
facility: Royal Perth
city: Randwick
country: Australia
facility: Princes of Wales Hospital
city: Shepparton
country: Australia
facility: Goulburn Valley Health
city: Sydney
country: Australia
facility: Westmead Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Poços De Caldas
country: Brazil
facility: Hospital do Coracao de Pocos de Caldas
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Calgary
country: Canada
facility: University of Calgary, O'Brien Institute for Public Health
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital & Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network (Toronto General Hospital)
state: Ontario
city: Montreal
country: Canada
facility: CHUM
state: Quebec
city: Sherbrooke
country: Canada
facility: Sherbrooke
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital (Saskatoon)
state: Saskatchewan
city: London
country: Canada
facility: Victoria Hospital
city: Santiago
country: Chile
facility: Clinica Santa Maria
city: Temuco
country: Chile
facility: Hospital Hernan Henriquez
city: Hefei
country: China
facility: Second Hospital of Anhui Medical University
state: Anhui
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
state: Capital Region
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Abdominal Centre
city: Køge
country: Denmark
facility: Zealand University Hospital
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint Joseph
city: Aachen
country: Germany
facility: University Hospital RWTH Aachen
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
city: Surat
country: India
facility: Surat Institute of Digestive Science
state: Gujarat
city: Vadodara
country: India
facility: Sumandeep Vidyapeeth & Dhiraj General Hospital
state: Gujurat
city: Shimoga
country: India
facility: Nanjappa Hospital
state: Karnataka
city: Trivandrum
country: India
facility: Government Medical College
state: Kerala
city: Nagpur
country: India
facility: Rahate Surgical Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Sengupta Hospital & Research Institute
state: Maharashtra
city: Pune
country: India
facility: AMAI Charitable Trust's Ace Hospital
state: Maharashtra
city: Doraha
country: India
facility: Sidhu Hospital Pvt. Ltd.
state: Punjab
city: Ludhiana
country: India
facility: Christian Medical College, Ludhiana
state: Punjab
city: Lucknow
country: India
facility: Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow
state: Uttar Pradesh
city: Kolkata
country: India
facility: NH Rabindranath Tagore International Inst. of Cardiac Sciences
state: West Bengal
city: Alappuzha
country: India
facility: TD Medical College
city: Bangalore
country: India
facility: Bangalore Baptist Hospital
city: Genova
country: Italy
facility: Ospedale Galliera di Genova
city: Milano
country: Italy
facility: IRCCS Galeazzi Orthopedic Institute
city: Milan
country: Italy
facility: Instituto Clinico San Siro
city: Milan
country: Italy
facility: IRCCS San Raffaele Scientific Institute
city: Port Dickson
country: Malaysia
facility: Port Dickson Hospital
state: Negeri Sembilan
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Sungai Buloh
country: Malaysia
facility: Sungai Buloh Hospital
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
state: Overijssel
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Grafton
country: New Zealand
facility: Auckland General Hospital
state: Auckland
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Hamilton
country: New Zealand
facility: Waikato District Health Board
city: Islamabad
country: Pakistan
facility: Shifa International Hospitals
state: Islamabad Capital Territory
city: Karachi
country: Pakistan
facility: Aga Khan University
city: Kraków
country: Poland
facility: Jagiellonian University Medical College
city: Tarnów
country: Poland
facility: Specialistyczny Szpital im. E. Szczeklika w Tarnowie
city: Zielona Góra
country: Poland
facility: Szpital Uniwersytecki im Karola Marcinkowskiego w Zielonej Górze
city: Arkhangelsk
country: Russian Federation
facility: City Hospital 1 of Arkhangelsk
city: Moscow
country: Russian Federation
facility: V. Negovskiy Reanimatology Research Institute
city: Moscow
country: Russian Federation
facility: Moscow Regional Research & Clinical Institute (MONIKI)
city: Novosibirsk
country: Russian Federation
facility: City Hospital N25
city: Novosibirsk
country: Russian Federation
facility: E. Meshalkin National Medical Research Center
city: Saint Petersburg
country: Russian Federation
facility: Hospital of Saint-Petersburg State University
city: Tyumen
country: Russian Federation
facility: Tyumen State Medical University
city: Observatory
country: South Africa
facility: Groote Schuur Hospital
state: Cape Town
city: Ga-Rankuwa
country: South Africa
facility: Sefako Makgatho Health Sciences University (SMU)
state: Gauteng
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital - University of Pretoria
state: Gauteng
city: Barcelona
country: Spain
facility: Hospital Clinic - Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Sta Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Girona
country: Spain
facility: Hospital Dr. Josep Trueta
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Alcorcon
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario in Valladolid
city: Gillingham
country: United Kingdom
facility: Medway NHS Foundation Trust
city: London
country: United Kingdom
facility: Chelsea & Westminster Hospital
city: London
country: United Kingdom
facility: West Middlesex Hospital
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: PJ Devereaux, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.