PeriOperative ISchemic Evaluation-3 Trial

Venous Thrombosis Clinical Trial

— POISE-3  

Official title:

PeriOperative ISchemic Evaluation-3 Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03505723
• Other study ID #: 2018.02.08
• Status: Completed
• Phase: Phase 3
• Start date: June 27, 2018
• Est. completion date: February 3, 2023

Study information

• Verified date: August 2023
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9535
• Est. completion date: February 3, 2023
• Est. primary completion date: November 8, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arterial Thrombosis
• Perioperative Bleeding
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Tranexamic Acid
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)
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.

Other:
• Perioperative hypotension-avoidance strategy
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 strategy
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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Eastern Health (Box Hill Hospital)	Box Hill	Victoria
Australia	Queen Elizabeth II Jubilee Hospital	Brisbane	Queensland
Australia	Dandenong Hospital	Dandenong	Victoria
Australia	Western Health	Footscray
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Peter MacCallum Hospital	Melbourne
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth	Perth
Australia	Princes of Wales Hospital	Randwick
Australia	Goulburn Valley Health	Shepparton
Australia	Westmead Hospital	Sydney
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medical University of Vienna	Vienna
Belgium	CHU Brugmann	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Brazil	Hospital do Coracao de Pocos de Caldas	Poços De Caldas	Minas Gerais
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
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	Juravinski Hospital & Cancer Centre	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Victoria Hospital	London
Canada	CHUM	Montreal	Quebec
Canada	Royal University Hospital (Saskatoon)	Saskatoon	Saskatchewan
Canada	Sherbrooke	Sherbrooke	Quebec
Canada	University Health Network (Toronto General Hospital)	Toronto	Ontario
Canada	Health Sciences Centre	Winnipeg	Manitoba
Chile	Clinica Santa Maria	Santiago
Chile	Hospital Hernan Henriquez	Temuco
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Second Hospital of Anhui Medical University	Hefei	Anhui
China	Shenzhen People's Hospital	Shenzhen	Guangdong
Denmark	Bispebjerg Hospital	Copenhagen	Capital Region
Denmark	Rigshospitalet, Abdominal Centre	Copenhagen
Denmark	Zealand University Hospital	Køge
France	Groupe Hospitalier Paris Saint Joseph	Paris
Germany	University Hospital RWTH Aachen	Aachen
Germany	University Hospital Bonn	Bonn
Germany	Klinikum Dortmund gGmbH	Dortmund
Germany	University Hospital Düsseldorf	Düsseldorf
Hong Kong	Prince of Wales Hospital	Sha Tin
India	TD Medical College	Alappuzha
India	Bangalore Baptist Hospital	Bangalore
India	Sidhu Hospital Pvt. Ltd.	Doraha	Punjab
India	NH Rabindranath Tagore International Inst. of Cardiac Sciences	Kolkata	West Bengal
India	Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow	Lucknow	Uttar Pradesh
India	Christian Medical College, Ludhiana	Ludhiana	Punjab
India	Rahate Surgical Hospital	Nagpur	Maharashtra
India	Sengupta Hospital & Research Institute	Nagpur	Maharashtra
India	AMAI Charitable Trust's Ace Hospital	Pune	Maharashtra
India	Nanjappa Hospital	Shimoga	Karnataka
India	Surat Institute of Digestive Science	Surat	Gujarat
India	Government Medical College	Trivandrum	Kerala
India	Sumandeep Vidyapeeth & Dhiraj General Hospital	Vadodara	Gujurat
Italy	Ospedale Galliera di Genova	Genova
Italy	Instituto Clinico San Siro	Milan
Italy	IRCCS San Raffaele Scientific Institute	Milan
Italy	IRCCS Galeazzi Orthopedic Institute	Milano
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Sarawak General Hospital	Kuching	Sarawak
Malaysia	Port Dickson Hospital	Port Dickson	Negeri Sembilan
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Malaysia	Sungai Buloh Hospital	Sungai Buloh
Netherlands	Deventer Ziekenhuis	Deventer	Overijssel
Netherlands	Erasmus University Medical Center	Rotterdam
New Zealand	Middlemore Hospital	Auckland
New Zealand	Auckland General Hospital	Grafton	Auckland
New Zealand	Waikato District Health Board	Hamilton
Pakistan	Shifa International Hospitals	Islamabad	Islamabad Capital Territory
Pakistan	Aga Khan University	Karachi
Poland	Jagiellonian University Medical College	Kraków
Poland	Specialistyczny Szpital im. E. Szczeklika w Tarnowie	Tarnów
Poland	Szpital Uniwersytecki im Karola Marcinkowskiego w Zielonej Górze	Zielona Góra
Russian Federation	City Hospital 1 of Arkhangelsk	Arkhangelsk
Russian Federation	Moscow Regional Research & Clinical Institute (MONIKI)	Moscow
Russian Federation	V. Negovskiy Reanimatology Research Institute	Moscow
Russian Federation	City Hospital N25	Novosibirsk
Russian Federation	E. Meshalkin National Medical Research Center	Novosibirsk
Russian Federation	Hospital of Saint-Petersburg State University	Saint Petersburg
Russian Federation	Tyumen State Medical University	Tyumen
South Africa	Sefako Makgatho Health Sciences University (SMU)	Ga-Rankuwa	Gauteng
South Africa	Groote Schuur Hospital	Observatory	Cape Town
South Africa	Steve Biko Academic Hospital - University of Pretoria	Pretoria	Gauteng
Spain	Hospital Clinic - Barcelona	Barcelona
Spain	Hospital de la Sta Creu i Sant Pau	Barcelona
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Hospital Dr. Josep Trueta	Girona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario Fundacion Alcorcon	Madrid
Spain	Hospital Clínico Universitario in Valladolid	Valladolid
United Kingdom	Medway NHS Foundation Trust	Gillingham
United Kingdom	Chelsea & Westminster Hospital	London
United Kingdom	West Middlesex Hospital	London
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cleveland Clinic - Fairview	Cleveland	Ohio
United States	Cleveland Clinic - Main Campus	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Cleveland Clinic - Hillcrest	Mayfield Heights	Ohio
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Cleveland Clinic, Florida	Weston	Florida
United States	Wake Forest	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Denmark,  France,  Germany,  Hong Kong,  India,  Italy,  Malaysia,  Netherlands,  New Zealand,  Pakistan,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Life threatening bleeding	Number of patients who experience a life threatening bleed.	30 days after randomization
Other	Major bleeding	Number of patients who experience a major bleed.	30 days after randomization
Other	Critical organ bleeding	Number of patients who experience bleeding in a critical organ.	30 days after randomization
Other	International Society on Thrombosis and Haemostasis (ISTH) major bleeding	Number of patients who experience an International Society on Thrombosis and Haemostasis (ISTH) major bleeding	30 days after randomization
Other	Non-hemorrhagic stroke	Number of patients who experience a non-hemorrhagic stroke	30 days after randomization
Other	Peripheral arterial thrombosis	Number of patients who experience peripheral arterial thrombosis	30 days after randomization
Other	Symptomatic proximal venous thromboembolism	Number of patients who experience a symptomatic proximal venous thromboembolism	30 days after randomization
Other	All-cause mortality	Number of patients who die of any cause	30 days after randomization
Other	Vascular mortality	Number of patients who die of vascular cause	30 days after randomization
Other	Hemorrhagic stroke	Number of patients who experience a hemorrhagic stroke	30 days after randomization
Other	Transfusion rate	Rate of transfusion in patients who experience a major bleeding event	30 days after randomization
Other	Cardiac revascularization	Number of patients who have undergo cardiac revascularization	30 days after randomization
Other	Amputation	Number of patients who have an amputation	30 days after randomization
Other	Symptomatic pulmonary embolism	Number of patients who experience a symptomatic pulmonary embolism	30 days after randomization
Other	Symptomatic proximal DVT	Number of patients who experience a symptomatic proximal DVT	30 days after randomization
Other	Any symptomatic or asymptomatic proximal venous thromboembolism	Number of patients who experience any (symptomatic or asymptomatic) proximal venous thromboembolism	30 days after randomization
Other	Acute kidney injury	Number of patients who experience an acute kidney injury	30 days after randomization
Other	New renal replacement therapy	Number of patients who require new renal replacement therapy	30 days after randomization
Other	Re-hospitalization for vascular reasons	Number of patients who experience a re-hospitalization for vascular reasons	30 days after randomization
Other	Seizures	Number of patients who experience a seizure	30 days after randomization
Other	Infection/sepsis	Number of patients who experience infection/sepsis	30 days after randomization
Other	Disability	Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).	30 days after randomization
Other	Length of hospital stay	Average length of hospital stay	30 days after randomization
Other	Days alive and at home	Number of days alive and at home	30 days after randomization
Other	For patients in the blood pressure management arm: vascular death	Number of patients who die from a vascular cause	30 days after randomization
Other	For patients in the blood pressure management arm: non-fatal MINS	Number of patients who experience a non-fatal MINS	30 days after randomization
Other	For patients in the blood pressure management arm: non-fatal stroke	Number of patients who experience a non-fatal stroke	30 days after randomization
Other	For patients in the blood pressure management arm: non-fatal cardiac arrest	Number of patients who experience non-fatal cardiac arrest	30 days after randomization
Other	For patients in the blood pressure management arm: hemorrhagic stroke	Number of patients who experience a hemorrhagic stroke	30 days after randomization
Other	For patients in the blood pressure management arm: non-hemorrhagic stroke	Number of patients who experience a non-hemorrhagic stroke	30 days after randomization
Other	For patients in the blood pressure management arm: acute kidney injury	Number of patients who experience an acute kidney injury	30 days after randomization
Other	For patients in the blood pressure management arm: new renal replacement therapy	Number of patients with new requirement for renal replacement therapy	30 days after randomization
Other	For patients in the blood pressure management arm: acute congestive heart failure	Number of patients who experience acute congestive heart failure	30 days after randomization
Other	For patients in the blood pressure management arm: new clinically important atrial fibrillation	Number of patients who experience new clinically important atrial fibrillation	30 days after randomization
Other	For patients in the blood pressure management arm: sepsis	Number of patients who experience a sepsis event	30 days after randomization
Other	For patients in the blood pressure management arm: disability	Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).	30 days after randomization
Other	For patients in the blood pressure management arm: cancellation/postponement of surgery on the day of surgery due to BP concerns	Number of patients whose surgery was cancelled/postponed on the day of surgery due to BP concerns	30 days after randomization
Other	For patients in the blood pressure management arm: length of hospital stay	Average length of hospital stay required	30 days after randomization
Other	For patients in the blood pressure management arm: days alive and at home	Number of days alive and at home	30 days after randomization
Other	All-cause mortality	Number of patients who die of any cause	1 year after randomization
Other	Vascular mortality	Number of patients who die of vascular cause	1 year after randomization
Other	Myocardial infarction	Number of patients who experience a myocardial infarction	1 year after randomization
Other	Cardiac arrest	Number of patients who experience cardiac arrest	1 year after randomization
Other	Hemorrhagic stroke	Number of patients who experience a hemorrhagic stroke	1 year after randomization
Other	Non-hemorrhagic stroke	Number of patients who experience a non-hemorrhagic stroke	1 year after randomization
Other	Peripheral arterial thrombosis	Number of patients who experience peripheral arterial thrombosis	1 year after randomization
Other	Amputation	Number of patients who had an amputation	1 year after randomization
Other	Symptomatic pulmonary embolism	Number of patients who experience a symptomatic pulmonary embolism	1 year after randomization
Other	Symptomatic proximal DVT	Number of patients who experience a symptomatic proximal DVT	1 year after randomization
Other	Symptomatic proximal venous thromboembolism	Number of patients who experience a symptomatic proximal venous thromboembolism	1 year after randomization
Other	Any symptomatic or asymptomatic proximal venous thromboembolism	Number of patients who experience any symptomatic or asymptomatic proximal venous thromboembolism	1 year after randomization
Other	New renal replacement therapy	Number of patients who require new renal replacement therapy	1 year after randomization
Other	Re-hospitalization for vascular reasons	Number of patients re-hospitalized for vascular reasons	1 year after randomization
Other	Seizures	Number of patients who experience a seizure	1 year after randomization
Other	Infection/sepsis	Number of patients who experience an infection and/or sepsis event	1 year after randomization
Other	Disability	Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).	1 year after randomization
Other	For patients in the blood pressure management arm: all-cause mortality	Number of patients who die of any cause	1 year after randomization
Other	For patients in the blood pressure management arm: vascular mortality	Number of patients who die of a vascular cause	1 year after randomization
Other	For patients in the blood pressure management arm: myocardial infarction	Number of patients who experience a myocardial infarction	1 year after randomization
Other	For patients in the blood pressure management arm: cardiac arrest	Number of patients who experience cardiac arrest	1 year after randomization
Other	For patients in the blood pressure management arm: hemorrhagic stroke	Number of patients who experience a hemorrhagic stroke	1 year after randomization
Other	For patients in the blood pressure management arm: non-hemorrhagic stroke	Number of patients who experience a non-hemorrhagic stroke	1 year after randomization
Other	For patients in the blood pressure management arm: new renal replacement therapy	Number of patients who require new renal replacement therapy	1 year after randomization
Other	For patients in the blood pressure management arm: acute congestive heart failure	Number of patients who experience acute congestive heart failure	1 year after randomization
Other	For patients in the blood pressure management arm: sepsis	Number of patients who experience a sepsis event	1 year after randomization
Other	For patients in the blood pressure management arm: Disability	Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).	1 year after randomization
Primary	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
Primary	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
Primary	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	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,	30 days after randomization
Secondary	BIMS	Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)	30 days after randomization
Secondary	MINS	Number of patients who experience a myocardial injury after noncardiac surgery (MINS)	30 days after randomization
Secondary	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	30 days after randomization
Secondary	Myocardial infarction	Number of patients who experience a myocardial infarction	30 days after randomization
Secondary	For patients in the blood pressure management arm: all-cause mortality	Number of patients who die of any cause	30 days after randomization
Secondary	For patients in the blood pressure management arm: MINS	Number of patients who experience a myocardial injury after noncardiac surgery (MINS)	30 days after randomization
Secondary	For patients in the blood pressure management arm: Myocardial infarction	Number of patients who experience a myocardial infarction	30 days after randomization
Secondary	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	30 days after randomization