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NCT Number: NCT03505723

PeriOperative ISchemic Evaluation-3 Trial

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.

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Key information

Conditions

Perioperative Bleeding Arterial Thrombosis Cardiovascular Diseases Embolism and Thrombosis Hypertension Hypotension Thrombosis Vascular Diseases Venous Thrombosis

Age range

45 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Queen Elizabeth II Jubilee Hospital, Brisbane, Queensland, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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):

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

  • 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

Treatment and study plan

Tranexamic Acid

Drug

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 (saline)

Drug

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

Perioperative hypotension-avoidance strategy

Other

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

Other

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.

Primary outcomes

  1. 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

  2. A composite of MINS, 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.

  3. For patients in the blood pressure management arm: A composite of vascular death, non-fatal MINS, 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, non-fatal myocardial injury after noncardiac surgery, non-fatal stroke, and non-fatal cardiac arrest.

Secondary outcomes

  1. 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

    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,

  2. BIMS

    Time frame: 30 days after randomization

    Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS)

  3. MINS

    Time frame: 30 days after randomization

    Number of patients who experience a myocardial injury after noncardiac surgery (MINS)

  4. MINS not fulfilling the 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

  5. Myocardial infarction

    Time frame: 30 days after randomization

    Number of patients who experience a myocardial infarction

  6. 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

  7. 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)

  8. For patients in the blood pressure management arm: Myocardial infarction

    Time frame: 30 days after randomization

    Number of patients who experience a myocardial infarction

  9. For patients in the blood pressure management arm: MINS not fulfilling the universal definition of myocardial infarction

    Time frame: 30 days after randomization

    Number of patients who experience MINS not fulfilling the universal definition of myocardial infarction

Other outcomes

  1. Life threatening bleeding

    Time frame: 30 days after randomization

    Number of patients who experience a life threatening bleed.

  2. Major bleeding

    Time frame: 30 days after randomization

    Number of patients who experience a major bleed.

  3. Critical organ bleeding

    Time frame: 30 days after randomization

    Number of patients who experience bleeding in a critical organ.

  4. International Society on Thrombosis and Haemostasis (ISTH) major bleeding

    Time frame: 30 days after randomization

    Number of patients who experience an International Society on Thrombosis and Haemostasis (ISTH) major bleeding

  5. Non-hemorrhagic stroke

    Time frame: 30 days after randomization

    Number of patients who experience a non-hemorrhagic stroke

  6. Peripheral arterial thrombosis

    Time frame: 30 days after randomization

    Number of patients who experience peripheral arterial thrombosis

  7. Symptomatic proximal venous thromboembolism

    Time frame: 30 days after randomization

    Number of patients who experience a symptomatic proximal venous thromboembolism

  8. All-cause mortality

    Time frame: 30 days after randomization

    Number of patients who die of any cause

  9. Vascular mortality

    Time frame: 30 days after randomization

    Number of patients who die of vascular cause

  10. Hemorrhagic stroke

    Time frame: 30 days after randomization

    Number of patients who experience a hemorrhagic stroke

  11. Transfusion rate

    Time frame: 30 days after randomization

    Rate of transfusion in patients who experience a major bleeding event

  12. Cardiac revascularization

    Time frame: 30 days after randomization

    Number of patients who have undergo cardiac revascularization

  13. Amputation

    Time frame: 30 days after randomization

    Number of patients who have an amputation

  14. Symptomatic pulmonary embolism

    Time frame: 30 days after randomization

    Number of patients who experience a symptomatic pulmonary embolism

  15. Symptomatic proximal DVT

    Time frame: 30 days after randomization

    Number of patients who experience a symptomatic proximal DVT

  16. 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

  17. Acute kidney injury

    Time frame: 30 days after randomization

    Number of patients who experience an acute kidney injury

  18. New renal replacement therapy

    Time frame: 30 days after randomization

    Number of patients who require new renal replacement therapy

  19. Re-hospitalization for vascular reasons

    Time frame: 30 days after randomization

    Number of patients who experience a re-hospitalization for vascular reasons

  20. Seizures

    Time frame: 30 days after randomization

    Number of patients who experience a seizure

  21. Infection/sepsis

    Time frame: 30 days after randomization

    Number of patients who experience infection/sepsis

  22. Disability

    Time frame: 30 days after randomization

    Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).

  23. Length of hospital stay

    Time frame: 30 days after randomization

    Average length of hospital stay

  24. Days alive and at home

    Time frame: 30 days after randomization

    Number of days alive and at home

  25. 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

  26. For patients in the blood pressure management arm: non-fatal MINS

    Time frame: 30 days after randomization

    Number of patients who experience a non-fatal MINS

  27. For patients in the blood pressure management arm: non-fatal stroke

    Time frame: 30 days after randomization

    Number of patients who experience a non-fatal stroke

  28. For patients in the blood pressure management arm: non-fatal cardiac arrest

    Time frame: 30 days after randomization

    Number of patients who experience non-fatal cardiac arrest

  29. For patients in the blood pressure management arm: hemorrhagic stroke

    Time frame: 30 days after randomization

    Number of patients who experience a hemorrhagic stroke

  30. 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

  31. 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

  32. 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

  33. 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

  34. For patients in the blood pressure management arm: new clinically important atrial fibrillation

    Time frame: 30 days after randomization

    Number of patients who experience new clinically important atrial fibrillation

  35. For patients in the blood pressure management arm: sepsis

    Time frame: 30 days after randomization

    Number of patients who experience a sepsis event

  36. 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]).

  37. 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

  38. For patients in the blood pressure management arm: length of hospital stay

    Time frame: 30 days after randomization

    Average length of hospital stay required

  39. 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

  40. All-cause mortality

    Time frame: 1 year after randomization

    Number of patients who die of any cause

  41. Vascular mortality

    Time frame: 1 year after randomization

    Number of patients who die of vascular cause

  42. Myocardial infarction

    Time frame: 1 year after randomization

    Number of patients who experience a myocardial infarction

  43. Cardiac arrest

    Time frame: 1 year after randomization

    Number of patients who experience cardiac arrest

  44. Hemorrhagic stroke

    Time frame: 1 year after randomization

    Number of patients who experience a hemorrhagic stroke

  45. Non-hemorrhagic stroke

    Time frame: 1 year after randomization

    Number of patients who experience a non-hemorrhagic stroke

  46. Peripheral arterial thrombosis

    Time frame: 1 year after randomization

    Number of patients who experience peripheral arterial thrombosis

  47. Amputation

    Time frame: 1 year after randomization

    Number of patients who had an amputation

  48. Symptomatic pulmonary embolism

    Time frame: 1 year after randomization

    Number of patients who experience a symptomatic pulmonary embolism

  49. Symptomatic proximal DVT

    Time frame: 1 year after randomization

    Number of patients who experience a symptomatic proximal DVT

  50. Symptomatic proximal venous thromboembolism

    Time frame: 1 year after randomization

    Number of patients who experience a symptomatic proximal venous thromboembolism

  51. 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

  52. New renal replacement therapy

    Time frame: 1 year after randomization

    Number of patients who require new renal replacement therapy

  53. Re-hospitalization for vascular reasons

    Time frame: 1 year after randomization

    Number of patients re-hospitalized for vascular reasons

  54. Seizures

    Time frame: 1 year after randomization

    Number of patients who experience a seizure

  55. Infection/sepsis

    Time frame: 1 year after randomization

    Number of patients who experience an infection and/or sepsis event

  56. Disability

    Time frame: 1 year after randomization

    Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).

  57. 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

  58. 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

  59. For patients in the blood pressure management arm: myocardial infarction

    Time frame: 1 year after randomization

    Number of patients who experience a myocardial infarction

  60. For patients in the blood pressure management arm: cardiac arrest

    Time frame: 1 year after randomization

    Number of patients who experience cardiac arrest

  61. For patients in the blood pressure management arm: hemorrhagic stroke

    Time frame: 1 year after randomization

    Number of patients who experience a hemorrhagic stroke

  62. 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

  63. 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

  64. 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

  65. For patients in the blood pressure management arm: sepsis

    Time frame: 1 year after randomization

    Number of patients who experience a sepsis event

  66. For patients in the blood pressure management arm: Disability

    Time frame: 1 year after randomization

    Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).

  67. For patients in the blood pressure management arm (CogPOISE-3 Sub study): Delirium

    Time frame: Post operative day one to three

    Number of patients who experience delirium (based on 3D-CAM or ICU-CAM)

  68. For patients in the blood pressure management arm (CogPOISE-3 Sub study): Cognitive decline

    Time frame: 1 year after randomization

    Number of patients who experience cognitive decline (at least 2 points decline on Montreal Cognitive Assessment MoCA) compared to assessment after consent and before randomization

Sponsors and collaborators

Lead sponsor

Population Health Research Institute

Other

Registry information

Acronym: POISE-3

Important dates

Study start
2018
Primary completion
2021
Study completion
2023
First posted
Apr 23, 2018
Registry last updated
Feb 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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