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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03505723




Registration number
NCT03505723
Ethics application status
Date submitted
16/03/2018
Date registered
23/04/2018
Date last updated
21/04/2020

Titles & IDs
Public title
PeriOperative ISchemic Evaluation-3 Trial
Scientific title
PeriOperative ISchemic Evaluation-3 Trial
Secondary ID [1] 0 0
2018.02.08
Universal Trial Number (UTN)
Trial acronym
POISE-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Perioperative Bleeding 0 0
Venous Thrombosis 0 0
Arterial Thrombosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Clotting disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tranexamic Acid
Treatment: Drugs - Placebo (Saline)
Other interventions - Perioperative hypotension-avoidance strategy
Other interventions - Perioperative hypertension-avoidance strategy

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).

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).

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).

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).


Treatment: Drugs: 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.

Treatment: Drugs: 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 interventions: 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.

Other interventions: 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.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
30 days after randomization
Primary outcome [2] 0 0
A composite of myocardial injury after noncardiac surgery, 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.
Timepoint [2] 0 0
30 days after randomization
Primary outcome [3] 0 0
For patients in the blood pressure management arm: A composite of vascular death, and non-fatal myocardial injury after noncardiac surgery, 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, and non-fatal myocardial injury after noncardiac surgery, non-fatal stroke, and non-fatal cardiac arrest.
Timepoint [3] 0 0
30 days after randomization
Secondary outcome [1] 0 0
A net risk-benefit outcome as a composite of 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 - 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,
Timepoint [1] 0 0
30 days after randomization
Secondary outcome [2] 0 0
International Society on Thrombosis and Haemostasis (ISTH) major bleeding - Number of patients who experience major bleeding (as defined by ISTH)
Timepoint [2] 0 0
30 days after randomization
Secondary outcome [3] 0 0
BIMS - Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)
Timepoint [3] 0 0
30 days after randomization
Secondary outcome [4] 0 0
MINS - Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
Timepoint [4] 0 0
30 days after randomization
Secondary outcome [5] 0 0
MINS not fulfilling the 3rd 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
Timepoint [5] 0 0
30 days after randomization
Secondary outcome [6] 0 0
Myocardial infarction - Number of patients who experience a myocardial infarction
Timepoint [6] 0 0
30 days after randomization
Secondary outcome [7] 0 0
For patients in the blood pressure management arm: all-cause mortality - Number of patients who die of any cause
Timepoint [7] 0 0
30 days after randomization
Secondary outcome [8] 0 0
For patients in the blood pressure management arm: MINS - Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
Timepoint [8] 0 0
30 days after randomization
Secondary outcome [9] 0 0
For patients in the blood pressure management arm: Myocardial infarction - Number of patients who experience a myocardial infarction
Timepoint [9] 0 0
30 days after randomization

Eligibility
Key inclusion 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.
Minimum age
45 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Eastern Health (Box Hill Hospital) - Box Hill
Recruitment hospital [6] 0 0
Dandenong Hospital - Dandenong
Recruitment hospital [7] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [9] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [10] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [11] 0 0
Western Health - Footscray
Recruitment hospital [12] 0 0
Mackay Base Hospital - Mackay
Recruitment hospital [13] 0 0
Peter MacCallum Hospital - Melbourne
Recruitment hospital [14] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [15] 0 0
Royal Perth - Perth
Recruitment hospital [16] 0 0
Princes of Wales Hospital - Randwick
Recruitment hospital [17] 0 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [18] 0 0
Goulburn Valley Health - Shepparton
Recruitment hospital [19] 0 0
Westmead Hospital - Sydney
Recruitment hospital [20] 0 0
Tweed Hospital - Tweed Heads
Recruitment postcode(s) [1] 0 0
- Woolloongabba
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Bedford Park
Recruitment postcode(s) [4] 0 0
- Hobart
Recruitment postcode(s) [5] 0 0
- Box Hill
Recruitment postcode(s) [6] 0 0
- Dandenong
Recruitment postcode(s) [7] 0 0
- Heidelberg
Recruitment postcode(s) [8] 0 0
- Parkville
Recruitment postcode(s) [9] 0 0
- Murdoch
Recruitment postcode(s) [10] 0 0
- Brisbane
Recruitment postcode(s) [11] 0 0
- Footscray
Recruitment postcode(s) [12] 0 0
- Mackay
Recruitment postcode(s) [13] 0 0
- Melbourne
Recruitment postcode(s) [14] 0 0
- New Lambton
Recruitment postcode(s) [15] 0 0
- Perth
Recruitment postcode(s) [16] 0 0
- Randwick
Recruitment postcode(s) [17] 0 0
- Redcliffe
Recruitment postcode(s) [18] 0 0
- Shepparton
Recruitment postcode(s) [19] 0 0
- Sydney
Recruitment postcode(s) [20] 0 0
- Tweed Heads
Recruitment outside Australia
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United States of America
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Connecticut
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United States of America
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Florida
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United States of America
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New York
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United States of America
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North Carolina
Country [5] 0 0
United States of America
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Ohio
Country [6] 0 0
United States of America
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Oregon
Country [7] 0 0
United States of America
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Pennsylvania
Country [8] 0 0
United States of America
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Texas
Country [9] 0 0
Austria
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Vienna
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Belgium
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Brussels
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Brazil
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Minas Gerais
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Brazil
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RS
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Brazil
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Porto Alegre
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Canada
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Alberta
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British Columbia
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Canada
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Manitoba
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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London
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Canada
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Toronto
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Chile
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Santiago
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Chile
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Temuco
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China
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Anhui
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Pisa
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Rivoli
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Rome
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Rozzano
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San Giovanni Rotondo
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Vimercate
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Negeri Sembilan
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Overijssel
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Rotterdam
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Auckland
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New Zealand
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Hamilton
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Islamabad Capital Territory
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Karachi
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Tarnów
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Zielona Góra
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Lódz
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Russian Federation
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Arkhangelsk
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Moscow
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Russian Federation
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Novosibirsk
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Russian Federation
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Saint Petersburg
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Russian Federation
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Tyumen
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Saudi Arabia
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Jeddah
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South Africa
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Cape Town
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South Africa
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Gauteng
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South Africa
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KwaZulu-Natal
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South Africa
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Pietermaritzburg
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Spain
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Barcelona
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Girona
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Madrid
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Spain
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Valladolid
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Switzerland
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Zürich
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Ashford
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Birmingham
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Blackburn
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Gillingham
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Liverpool
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Manchester
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Oxford
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United Kingdom
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York

Funding & Sponsors
Primary sponsor type
Other
Name
Population Health Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03505723
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
PJ Devereaux, MD, PhD
Address 0 0
Hamilton Health Sciences Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jessica Vincent, MSc
Address 0 0
Country 0 0
Phone 0 0
905-297-3479
Fax 0 0
Email 0 0
Jessica.Vincent@phri.ca
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03505723