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PeriOperative ISchemic Evaluation-3 Trial (POISE-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03505723
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
P.J. Devereaux, Population Health Research Institute

Tracking Information
First Submitted Date  ICMJE March 16, 2018
First Posted Date  ICMJE April 23, 2018
Last Update Posted Date April 21, 2020
Actual Study Start Date  ICMJE June 27, 2018
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • A composite of life-threatening bleeding, major bleeding, and critical organ bleeding [ Time Frame: 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 myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism. [ Time Frame: 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, and non-fatal myocardial injury after noncardiac surgery, non-fatal stroke, and non-fatal cardiac arrest. [ Time Frame: 30 days after randomization ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 13, 2018)
  • A composite of life-threatening bleeding, major bleeding, and critical organ bleeding [ Time Frame: 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 myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism. [ Time Frame: 30 days after randomization ]
    Number of patients who have at least one of the following: myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism.
  • For patients in the blood pressure management arm: A composite of vascular death, and non-fatal myocardial infarction, stroke, and cardiac arrest. [ Time Frame: 30 days after randomization ]
    Number of patients enrolled in the blood pressure management arm who have at least one of the following: vascular death, and non-fatal myocardial infarction, stroke, and cardiac arrest.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • 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 [ Time Frame: 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,
  • International Society on Thrombosis and Haemostasis (ISTH) major bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience major bleeding (as defined by ISTH)
  • BIMS [ Time Frame: 30 days after randomization ]
    Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)
  • MINS [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
  • MINS not fulfilling the 3rd universal definition of myocardial infarction [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial infarction
  • For patients in the blood pressure management arm: all-cause mortality [ Time Frame: 30 days after randomization ]
    Number of patients who die of any cause
  • For patients in the blood pressure management arm: MINS [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial infarction
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2018)
  • A net risk-benefit outcome as a composite of vascular death, and non-fatal life-threatening, major or critical organ bleeding, MI, stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism. [ Time Frame: 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 infarction, stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism,
  • International Society on Thrombosis and Haemostasis (ISTH) major bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience major bleeding (as defined by ISTH)
  • BIMS [ Time Frame: 30 days after randomization ]
    Number of patients who experience bleeding impacting mortality after noncardiac surgery (BIMS)
  • MINS [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial injury after noncardiac surgery (MINS)
  • Myocardial infarction [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial infarction
  • For patients in the blood pressure management arm: all-cause mortality [ Time Frame: 30 days after randomization ]
    Number of patients who die of any cause
  • For patients in the blood pressure management arm: MINS [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial infarction
Current Other Pre-specified Outcome Measures
 (submitted: April 17, 2020)
  • Life threatening bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience a life threatening bleed.
  • Major bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience a major bleed.
  • Critical organ bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience bleeding in a critical organ.
  • Non-hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a non-hemorrhagic stroke
  • Peripheral arterial thrombosis [ Time Frame: 30 days after randomization ]
    Number of patients who experience peripheral arterial thrombosis
  • Symptomatic proximal venous thromboembolism [ Time Frame: 30 days after randomization ]
    Number of patients who experience a symptomatic proximal venous thromboembolism
  • All-cause mortality [ Time Frame: 30 days after randomization ]
    Number of patients who die of any cause
  • Vascular mortality [ Time Frame: 30 days after randomization ]
    Number of patients who die of vascular cause
  • Hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • Transfusion rate [ Time Frame: 30 days after randomization ]
    Rate of transfusion in patients who experience a major bleeding event
  • Cardiac revascularization [ Time Frame: 30 days after randomization ]
    Number of patients who have undergo cardiac revascularization
  • Amputation [ Time Frame: 30 days after randomization ]
    Number of patients who have an amputation
  • Symptomatic pulmonary embolism [ Time Frame: 30 days after randomization ]
    Number of patients who experience a symptomatic pulmonary embolism
  • Symptomatic proximal DVT [ Time Frame: 30 days after randomization ]
    Number of patients who experience a symptomatic proximal DVT
  • Any symptomatic or asymptomatic proximal venous thromboembolism [ Time Frame: 30 days after randomization ]
    Number of patients who experience any (symptomatic or asymptomatic) proximal venous thromboembolism
  • Acute kidney injury [ Time Frame: 30 days after randomization ]
    Number of patients who experience an acute kidney injury
  • New renal replacement therapy [ Time Frame: 30 days after randomization ]
    Number of patients who require new renal replacement therapy
  • Re-hospitalization for vascular reasons [ Time Frame: 30 days after randomization ]
    Number of patients who experience a re-hospitalization for vascular reasons
  • Seizures [ Time Frame: 30 days after randomization ]
    Number of patients who experience a seizure
  • Infection/sepsis [ Time Frame: 30 days after randomization ]
    Number of patients who experience infection/sepsis
  • Disability [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Average length of hospital stay
  • Days alive and at home [ Time Frame: 30 days after randomization ]
    Number of days alive and at home
  • For patients in the blood pressure management arm: vascular death [ Time Frame: 30 days after randomization ]
    Number of patients who die from a vascular cause
  • For patients in the blood pressure management arm: non-fatal myocardial infarction [ Time Frame: 30 days after randomization ]
    Number of patients who experience a non-fatal myocardial infarction
  • For patients in the blood pressure management arm: stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a stroke
  • For patients in the blood pressure management arm: cardiac arrest [ Time Frame: 30 days after randomization ]
    Number of patients who experience cardiac arrest
  • For patients in the blood pressure management arm: hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • For patients in the blood pressure management arm: non-hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a non-hemorrhagic stroke
  • For patients in the blood pressure management arm: acute kidney injury [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Number of patients who experience acute congestive heart failure
  • For patients in the blood pressure management arm: new onset atrial fibrillation [ Time Frame: 30 days after randomization ]
    Number of patients who experience new onset of atrial fibrillation
  • For patients in the blood pressure management arm: sepsis [ Time Frame: 30 days after randomization ]
    Number of patients who experience a sepsis event
  • For patients in the blood pressure management arm: disability [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Average length of hospital stay required
  • For patients in the blood pressure management arm: days alive and at home [ Time Frame: 30 days after randomization ]
    Number of days alive and at home
  • All-cause mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of any cause
  • Vascular mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of vascular cause
  • Myocardial infarction [ Time Frame: 1 year after randomization ]
    Number of patients who experience a myocardial infarction
  • Cardiac arrest [ Time Frame: 1 year after randomization ]
    Number of patients who experience cardiac arrest
  • Hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • Non-hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a non-hemorrhagic stroke
  • Peripheral arterial thrombosis [ Time Frame: 1 year after randomization ]
    Number of patients who experience peripheral arterial thrombosis
  • Amputation [ Time Frame: 1 year after randomization ]
    Number of patients who had an amputation
  • Symptomatic pulmonary embolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic pulmonary embolism
  • Symptomatic proximal DVT [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic proximal DVT
  • Symptomatic proximal venous thromboembolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic proximal venous thromboembolism
  • Any symptomatic or asymptomatic proximal venous thromboembolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience any symptomatic or asymptomatic proximal venous thromboembolism
  • New renal replacement therapy [ Time Frame: 1 year after randomization ]
    Number of patients who require new renal replacement therapy
  • Re-hospitalization for vascular reasons [ Time Frame: 1 year after randomization ]
    Number of patients re-hospitalized for vascular reasons
  • Seizures [ Time Frame: 1 year after randomization ]
    Number of patients who experience a seizure
  • Infection/sepsis [ Time Frame: 1 year after randomization ]
    Number of patients who experience an infection and/or sepsis event
  • Disability [ Time Frame: 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 [ Time Frame: 1 year after randomization ]
    Number of patients who die of any cause
  • For patients in the blood pressure management arm: vascular mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of a vascular cause
  • For patients in the blood pressure management arm: myocardial infarction [ Time Frame: 1 year after randomization ]
    Number of patients who experience a myocardial infarction
  • For patients in the blood pressure management arm: cardiac arrest [ Time Frame: 1 year after randomization ]
    Number of patients who experience cardiac arrest
  • For patients in the blood pressure management arm: hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • For patients in the blood pressure management arm: non-hemorrhagic stroke [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 year after randomization ]
    Number of patients who experience acute congestive heart failure
  • For patients in the blood pressure management arm: sepsis [ Time Frame: 1 year after randomization ]
    Number of patients who experience a sepsis event
  • For patients in the blood pressure management arm: [ Time Frame: 1 year after randomization ]
    Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).
Original Other Pre-specified Outcome Measures
 (submitted: April 13, 2018)
  • Life threatening bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience a life threatening bleed.
  • Major bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience a major bleed.
  • Critical organ bleeding [ Time Frame: 30 days after randomization ]
    Number of patients who experience bleeding in a critical organ.
  • Myocardial infarction [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial infarction
  • Non-hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a non-hemorrhagic stroke
  • Peripheral arterial thrombosis [ Time Frame: 30 days after randomization ]
    Number of patients who experience peripheral arterial thrombosis
  • Symptomatic proximal venous thromboembolism [ Time Frame: 30 days after randomization ]
    Number of patients who experience a symptomatic proximal venous thromboembolism
  • All-cause mortality [ Time Frame: 30 days after randomization ]
    Number of patients who die of any cause
  • Vascular mortality [ Time Frame: 30 days after randomization ]
    Number of patients who die of vascular cause
  • Hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • Transfusion rate [ Time Frame: 30 days after randomization ]
    Rate of transfusion in patients who experience a major bleeding event
  • Cardiac revascularization [ Time Frame: 30 days after randomization ]
    Number of patients who have undergo cardiac revascularization
  • Amputation [ Time Frame: 30 days after randomization ]
    Number of patients who have an amputation
  • Symptomatic pulmonary embolism [ Time Frame: 30 days after randomization ]
    Number of patients who experience a symptomatic pulmonary embolism
  • Symptomatic proximal DVT [ Time Frame: 30 days after randomization ]
    Number of patients who experience a symptomatic proximal DVT
  • Any symptomatic or asymptomatic proximal venous thromboembolism [ Time Frame: 30 days after randomization ]
    Number of patients who experience any (symptomatic or asymptomatic) proximal venous thromboembolism
  • Acute kidney injury [ Time Frame: 30 days after randomization ]
    Number of patients who experience an acute kidney injury
  • New renal replacement therapy [ Time Frame: 30 days after randomization ]
    Number of patients who require new renal replacement therapy
  • Re-hospitalization for vascular reasons [ Time Frame: 30 days after randomization ]
    Number of patients who experience a re-hospitalization for vascular reasons
  • Seizures [ Time Frame: 30 days after randomization ]
    Number of patients who experience a seizure
  • Infection/sepsis [ Time Frame: 30 days after randomization ]
    Number of patients who experience infection/sepsis
  • Disability [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Average length of hospital stay
  • For patients in the blood pressure management arm: vascular death [ Time Frame: 30 days after randomization ]
    Number of patients who die from a vascular cause
  • For patients in the blood pressure management arm: non-fatal myocardial infarction [ Time Frame: 30 days after randomization ]
    Number of patients who experience a non-fatal myocardial infarction
  • For patients in the blood pressure management arm: stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a stroke
  • For patients in the blood pressure management arm: cardiac arrest [ Time Frame: 30 days after randomization ]
    Number of patients who experience cardiac arrest
  • For patients in the blood pressure management arm: hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • For patients in the blood pressure management arm: non-hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a non-hemorrhagic stroke
  • For patients in the blood pressure management arm: acute kidney injury [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Number of patients who experience acute congestive heart failure
  • For patients in the blood pressure management arm: new onset atrial fibrillation [ Time Frame: 30 days after randomization ]
    Number of patients who experience new onset of atrial fibrillation
  • For patients in the blood pressure management arm: sepsis [ Time Frame: 30 days after randomization ]
    Number of patients who experience a sepsis event
  • For patients in the blood pressure management arm: disability [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 30 days after randomization ]
    Average length of hospital stay required
  • All-cause mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of any cause
  • Vascular mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of vascular cause
  • Myocardial infarction [ Time Frame: 1 year after randomization ]
    Number of patients who experience a myocardial infarction
  • Cardiac arrest [ Time Frame: 1 year after randomization ]
    Number of patients who experience cardiac arrest
  • Hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • Non-hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a non-hemorrhagic stroke
  • Peripheral arterial thrombosis [ Time Frame: 1 year after randomization ]
    Number of patients who experience peripheral arterial thrombosis
  • Amputation [ Time Frame: 1 year after randomization ]
    Number of patients who had an amputation
  • Symptomatic pulmonary embolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic pulmonary embolism
  • Symptomatic proximal DVT [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic proximal DVT
  • Symptomatic proximal venous thromboembolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic proximal venous thromboembolism
  • Any symptomatic or asymptomatic proximal venous thromboembolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience any symptomatic or asymptomatic proximal venous thromboembolism
  • New renal replacement therapy [ Time Frame: 1 year after randomization ]
    Number of patients who require new renal replacement therapy
  • Re-hospitalization for vascular reasons [ Time Frame: 1 year after randomization ]
    Number of patients re-hospitalized for vascular reasons
  • Seizures [ Time Frame: 1 year after randomization ]
    Number of patients who experience a seizure
  • Infection/sepsis [ Time Frame: 1 year after randomization ]
    Number of patients who experience an infection and/or sepsis event
  • Disability [ Time Frame: 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 [ Time Frame: 1 year after randomization ]
    Number of patients who die of any cause
  • For patients in the blood pressure management arm: vascular mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of a vascular cause
  • For patients in the blood pressure management arm: myocardial infarction [ Time Frame: 1 year after randomization ]
    Number of patients who experience a myocardial infarction
  • For patients in the blood pressure management arm: cardiac arrest [ Time Frame: 1 year after randomization ]
    Number of patients who experience cardiac arrest
  • For patients in the blood pressure management arm: hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a hemorrhagic stroke
  • For patients in the blood pressure management arm: non-hemorrhagic stroke [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 year after randomization ]
    Number of patients who experience acute congestive heart failure
  • For patients in the blood pressure management arm: sepsis [ Time Frame: 1 year after randomization ]
    Number of patients who experience a sepsis event
  • For patients in the blood pressure management arm: [ Time Frame: 1 year after randomization ]
    Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).
 
Descriptive Information
Brief Title  ICMJE PeriOperative ISchemic Evaluation-3 Trial
Official Title  ICMJE PeriOperative ISchemic Evaluation-3 Trial
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Perioperative Bleeding
  • Venous Thrombosis
  • Arterial Thrombosis
Intervention  ICMJE
  • 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 Name: TXA
  • 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 Name: saline
  • Other: Perioperative hypotension-avoidance strategy

    Perioperative hypotension-avoidance strategy includes:

    1. Preoperative algorithm that only continues some antihypertensive medications in a stepwise manner for systolic BP ≥130 mm Hg before surgery,
    2. Intraoperative blood pressure targeting a mean arterial pressure (MAP) ≥80 mm Hg
    3. 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: 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.
Study Arms  ICMJE
  • 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).
    Intervention: Drug: Tranexamic Acid
  • 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).
    Intervention: Drug: Placebo (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).
    Intervention: Other: Perioperative hypotension-avoidance strategy
  • 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).
    Intervention: Other: Perioperative hypertension-avoidance strategy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 13, 2018)
10000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Jessica Vincent, MSc 905-297-3479 ext 40635 Jessica.Vincent@phri.ca
Contact: Ingrid Copland 905-297-3479 ext 40368 ingrid.copland@phri.ca
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   China,   Denmark,   France,   Germany,   Hong Kong,   India,   Ireland,   Italy,   Malaysia,   Netherlands,   New Zealand,   Pakistan,   Poland,   Russian Federation,   Saudi Arabia,   South Africa,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries Romania,   Uganda,   United Arab Emirates
 
Administrative Information
NCT Number  ICMJE NCT03505723
Other Study ID Numbers  ICMJE 2018.02.08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party P.J. Devereaux, Population Health Research Institute
Study Sponsor  ICMJE Population Health Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: PJ Devereaux, MD, PhD Hamilton Health Sciences Corporation
PRS Account Population Health Research Institute
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP