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PeriOperative ISchemic Evaluation-3 Trial (POISE-3)

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ClinicalTrials.gov Identifier: NCT03505723
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
P.J. Devereaux, Population Health Research Institute

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10000 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 : July 30, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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:

  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.

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.




Primary Outcome Measures :
  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 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.

  3. 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.


Secondary Outcome Measures :
  1. 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,

  2. 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)

  3. BIMS [ Time Frame: 30 days after randomization ]
    Number of patients who experience bleeding impacting mortality after noncardiac surgery (BIMS)

  4. MINS [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial injury after noncardiac surgery (MINS)

  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


Other Outcome Measures:
  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. Myocardial infarction [ Time Frame: 30 days after randomization ]
    Number of patients who experience a myocardial infarction

  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. 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

  25. 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

  26. For patients in the blood pressure management arm: stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a stroke

  27. For patients in the blood pressure management arm: cardiac arrest [ Time Frame: 30 days after randomization ]
    Number of patients who experience cardiac arrest

  28. For patients in the blood pressure management arm: hemorrhagic stroke [ Time Frame: 30 days after randomization ]
    Number of patients who experience a hemorrhagic stroke

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. For patients in the blood pressure management arm: sepsis [ Time Frame: 30 days after randomization ]
    Number of patients who experience a sepsis event

  35. 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]).

  36. 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

  37. For patients in the blood pressure management arm: length of hospital stay [ Time Frame: 30 days after randomization ]
    Average length of hospital stay required

  38. All-cause mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of any cause

  39. Vascular mortality [ Time Frame: 1 year after randomization ]
    Number of patients who die of vascular cause

  40. Myocardial infarction [ Time Frame: 1 year after randomization ]
    Number of patients who experience a myocardial infarction

  41. Cardiac arrest [ Time Frame: 1 year after randomization ]
    Number of patients who experience cardiac arrest

  42. Hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a hemorrhagic stroke

  43. Non-hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a non-hemorrhagic stroke

  44. Peripheral arterial thrombosis [ Time Frame: 1 year after randomization ]
    Number of patients who experience peripheral arterial thrombosis

  45. Amputation [ Time Frame: 1 year after randomization ]
    Number of patients who had an amputation

  46. Symptomatic pulmonary embolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic pulmonary embolism

  47. Symptomatic proximal DVT [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic proximal DVT

  48. Symptomatic proximal venous thromboembolism [ Time Frame: 1 year after randomization ]
    Number of patients who experience a symptomatic proximal venous thromboembolism

  49. 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

  50. New renal replacement therapy [ Time Frame: 1 year after randomization ]
    Number of patients who require new renal replacement therapy

  51. Re-hospitalization for vascular reasons [ Time Frame: 1 year after randomization ]
    Number of patients re-hospitalized for vascular reasons

  52. Seizures [ Time Frame: 1 year after randomization ]
    Number of patients who experience a seizure

  53. Infection/sepsis [ Time Frame: 1 year after randomization ]
    Number of patients who experience an infection and/or sepsis event

  54. Disability [ Time Frame: 1 year after randomization ]
    Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule [WHODAS 2.0]).

  55. 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

  56. 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

  57. For patients in the blood pressure management arm: myocardial infarction [ Time Frame: 1 year after randomization ]
    Number of patients who experience a myocardial infarction

  58. For patients in the blood pressure management arm: cardiac arrest [ Time Frame: 1 year after randomization ]
    Number of patients who experience cardiac arrest

  59. For patients in the blood pressure management arm: hemorrhagic stroke [ Time Frame: 1 year after randomization ]
    Number of patients who experience a hemorrhagic stroke

  60. 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

  61. 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

  62. 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

  63. For patients in the blood pressure management arm: sepsis [ Time Frame: 1 year after randomization ]
    Number of patients who experience a sepsis event

  64. 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]).



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Exclusion criteria:

  1. Planned use of systemic TXA during surgery
  2. Hypersensitivity or known allergy to TXA
  3. Creatinine clearance <30 mL/min (Modification of Diet in Renal Disease [MDRD])
  4. History of seizure disorder
  5. Patients with recent stroke, myocardial infarction, acute arterial thrombosis or venous thromboembolism (<1 month)
  6. Patients with subarachnoid hemorrhage within the past 30 days
  7. Patients undergoing cranial neurosurgery
  8. Previously enrolled in POISE-3 Trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03505723


Contacts
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Contact: Jessica Vincent, MSc 905-527-4322 ext 40635 Jessica.Vincent@phri.ca

  Show 139 Study Locations
Sponsors and Collaborators
Population Health Research Institute
Investigators
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Principal Investigator: PJ Devereaux, MD, PhD Hamilton Health Sciences Corporation

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Responsible Party: P.J. Devereaux, Professor, Principal Investigator, Population Health Research Institute
ClinicalTrials.gov Identifier: NCT03505723     History of Changes
Other Study ID Numbers: 2018.02.16
First Posted: April 23, 2018    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018

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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

Keywords provided by P.J. Devereaux, Population Health Research Institute:
Noncardiac surgery
Myocardial injury
Perioperative myocardial infarction
Tranexamic Acid
Hypotension
Hypertension

Additional relevant MeSH terms:
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Thrombosis
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants