POISE-3: PeriOperative ISchemic Evaluation-3 Trial

Sponsor

Population Health Research Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03505723

Collaborator

(none)

9,535

Enrollment

114

Locations

Arms

53.2

Anticipated Duration (Months)

83.6

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Perioperative Bleeding Venous Thrombosis Arterial Thrombosis	Drug: Tranexamic Acid Drug: Placebo (Saline) Other: Perioperative hypotension-avoidance strategy Other: Perioperative hypertension-avoidance strategy	Phase 3

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

Study Type:

Interventional

Actual Enrollment :

9535 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

PeriOperative ISchemic Evaluation-3 Trial

Actual Study Start Date :

Jun 27, 2018

Actual Primary Completion Date :

Nov 8, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tranexamic Acid (TXA) Patients will receive a 1g loading dose of intravenous TXA before surgery and a 1g loading dose of intravenous TXA at the end of surgery (wound closure).	Drug: Tranexamic Acid 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. Other Names: TXA
Placebo Comparator: Placebo (0.9% normal 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).	Drug: 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 Names: saline
Active Comparator: 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).	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.
Placebo Comparator: 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).	Other: 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.

Outcome Measures

Primary Outcome Measures

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

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

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;

Undergoing emergent/urgent surgery.

Exclusion criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital	New Haven	Connecticut	United States	06510
2	Cleveland Clinic, Florida	Weston	Florida	United States	33331
3	Columbia University	New York	New York	United States	10027
4	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7010
5	Wake Forest	Winston-Salem	North Carolina	United States	27157
6	Cleveland Clinic - Fairview	Cleveland	Ohio	United States	44111
7	Cleveland Clinic - Main Campus	Cleveland	Ohio	United States	44195
8	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
9	Cleveland Clinic - Hillcrest	Mayfield Heights	Ohio	United States	44124
10	Oregon Health & Science University	Portland	Oregon	United States	97239
11	Rhode Island Hospital	Providence	Rhode Island	United States	02903
12	MD Anderson Cancer Center	Houston	Texas	United States	77030
13	Queen Elizabeth II Jubilee Hospital	Brisbane	Queensland	Australia	4108
14	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia
15	Royal Adelaide Hospital	Adelaide	South Australia	Australia
16	Flinders Medical Centre	Bedford Park	South Australia	Australia
17	Royal Hobart Hospital	Hobart	Tasmania	Australia
18	Eastern Health (Box Hill Hospital)	Box Hill	Victoria	Australia
19	Dandenong Hospital	Dandenong	Victoria	Australia
20	Austin Hospital	Heidelberg	Victoria	Australia
21	Royal Melbourne Hospital	Parkville	Victoria	Australia
22	Fiona Stanley Hospital	Murdoch	Western Australia	Australia
23	Western Health	Footscray		Australia
24	Peter MacCallum Hospital	Melbourne		Australia
25	John Hunter Hospital	New Lambton		Australia
26	Royal Perth	Perth		Australia
27	Princes of Wales Hospital	Randwick		Australia
28	Goulburn Valley Health	Shepparton		Australia
29	Westmead Hospital	Sydney		Australia
30	Medical University of Vienna	Vienna		Austria
31	CHU Brugmann	Brussels		Belgium
32	Cliniques Universitaires Saint-Luc	Brussels		Belgium
33	Hospital do Coracao de Pocos de Caldas	Poços De Caldas	Minas Gerais	Brazil
34	Hospital de Clinicas de Porto Alegre	Porto Alegre		Brazil
35	University of Calgary, O'Brien Institute for Public Health	Calgary	Alberta	Canada
36	University of Alberta	Edmonton	Alberta	Canada
37	Health Sciences Centre	Winnipeg	Manitoba	Canada
38	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2
39	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N 4A6
40	Juravinski Hospital & Cancer Centre	Hamilton	Ontario	Canada	L8V 1C3
41	Kingston Health Sciences Centre	Kingston	Ontario	Canada
42	University Health Network (Toronto General Hospital)	Toronto	Ontario	Canada
43	CHUM	Montreal	Quebec	Canada
44	Sherbrooke	Sherbrooke	Quebec	Canada
45	Royal University Hospital (Saskatoon)	Saskatoon	Saskatchewan	Canada
46	Victoria Hospital	London		Canada
47	Clinica Santa Maria	Santiago		Chile
48	Hospital Hernan Henriquez	Temuco		Chile
49	Second Hospital of Anhui Medical University	Hefei	Anhui	China
50	Shenzhen People's Hospital	Shenzhen	Guangdong	China
51	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang	China
52	West China Hospital of Sichuan University	Chengdu	Sichuan	China
53	Bispebjerg Hospital	Copenhagen	Capital Region	Denmark
54	Rigshospitalet, Abdominal Centre	Copenhagen		Denmark
55	Zealand University Hospital	Køge		Denmark
56	Groupe Hospitalier Paris Saint Joseph	Paris		France
57	University Hospital RWTH Aachen	Aachen		Germany
58	University Hospital Bonn	Bonn		Germany
59	Klinikum Dortmund gGmbH	Dortmund		Germany
60	University Hospital Düsseldorf	Düsseldorf		Germany
61	Prince of Wales Hospital	Sha Tin		Hong Kong
62	Surat Institute of Digestive Science	Surat	Gujarat	India
63	Sumandeep Vidyapeeth & Dhiraj General Hospital	Vadodara	Gujurat	India
64	Nanjappa Hospital	Shimoga	Karnataka	India
65	Government Medical College	Trivandrum	Kerala	India	695011
66	Rahate Surgical Hospital	Nagpur	Maharashtra	India
67	Sengupta Hospital & Research Institute	Nagpur	Maharashtra	India
68	AMAI Charitable Trust's Ace Hospital	Pune	Maharashtra	India
69	Sidhu Hospital Pvt. Ltd.	Doraha	Punjab	India
70	Christian Medical College, Ludhiana	Ludhiana	Punjab	India
71	Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow	Lucknow	Uttar Pradesh	India
72	NH Rabindranath Tagore International Inst. of Cardiac Sciences	Kolkata	West Bengal	India	700099
73	TD Medical College	Alappuzha		India
74	Bangalore Baptist Hospital	Bangalore		India
75	Ospedale Galliera di Genova	Genova		Italy
76	IRCCS Galeazzi Orthopedic Institute	Milano		Italy
77	Instituto Clinico San Siro	Milan		Italy
78	IRCCS San Raffaele Scientific Institute	Milan		Italy
79	Port Dickson Hospital	Port Dickson	Negeri Sembilan	Malaysia
80	Sarawak General Hospital	Kuching	Sarawak	Malaysia
81	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia
82	University Malaya Medical Centre	Kuala Lumpur		Malaysia
83	Hospital Pulau Pinang	Pulau Pinang		Malaysia
84	Sungai Buloh Hospital	Sungai Buloh		Malaysia
85	Deventer Ziekenhuis	Deventer	Overijssel	Netherlands
86	Erasmus University Medical Center	Rotterdam		Netherlands
87	Auckland General Hospital	Grafton	Auckland	New Zealand
88	Middlemore Hospital	Auckland		New Zealand
89	Waikato District Health Board	Hamilton		New Zealand
90	Shifa International Hospitals	Islamabad	Islamabad Capital Territory	Pakistan
91	Aga Khan University	Karachi		Pakistan
92	Jagiellonian University Medical College	Kraków		Poland
93	Specialistyczny Szpital im. E. Szczeklika w Tarnowie	Tarnów		Poland
94	Szpital Uniwersytecki im Karola Marcinkowskiego w Zielonej Górze	Zielona Góra		Poland
95	City Hospital 1 of Arkhangelsk	Arkhangelsk		Russian Federation
96	V. Negovskiy Reanimatology Research Institute	Moscow		Russian Federation	107031
97	Moscow Regional Research & Clinical Institute (MONIKI)	Moscow		Russian Federation
98	City Hospital N25	Novosibirsk		Russian Federation
99	E. Meshalkin National Medical Research Center	Novosibirsk		Russian Federation
100	Hospital of Saint-Petersburg State University	Saint Petersburg		Russian Federation
101	Tyumen State Medical University	Tyumen		Russian Federation
102	Groote Schuur Hospital	Observatory	Cape Town	South Africa
103	Sefako Makgatho Health Sciences University (SMU)	Ga-Rankuwa	Gauteng	South Africa
104	Steve Biko Academic Hospital - University of Pretoria	Pretoria	Gauteng	South Africa
105	Hospital Clinic - Barcelona	Barcelona		Spain
106	Hospital de la Sta Creu i Sant Pau	Barcelona		Spain
107	Hospital Vall D'Hebron	Barcelona		Spain
108	Hospital Dr. Josep Trueta	Girona		Spain
109	Hospital Ramon y Cajal	Madrid		Spain
110	Hospital Universitario Fundacion Alcorcon	Madrid		Spain
111	Hospital Clínico Universitario in Valladolid	Valladolid		Spain
112	Medway NHS Foundation Trust	Gillingham		United Kingdom
113	Chelsea & Westminster Hospital	London		United Kingdom
114	West Middlesex Hospital	London		United Kingdom