Arterial Thrombosis, Perioperative Bleeding, Venous Thrombosis
Conditions
Keywords
Noncardiac surgery, Myocardial injury, Perioperative myocardial infarction, Tranexamic Acid, Hypotension, Hypertension
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.
Interventions
DRUGTranexamic 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.
DRUGPlacebo (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.
OTHERPerioperative 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.
OTHERPerioperative 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.
Sponsors
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A composite of life-threatening bleeding, major bleeding, and critical organ bleeding | 30 days after randomization | Number of patients who have at least one of the following: life-threatening bleeding, major bleeding, and critical organ bleeding |
| A composite of MINS, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism. | 30 days after randomization | Number of patients who have at least one of the following: myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism. |
| For patients in the blood pressure management arm: A composite of vascular death, non-fatal MINS, non-fatal stroke, and non-fatal cardiac arrest. | 30 days after randomization | Number of patients enrolled in the blood pressure management arm who have at least one of the following: vascular death, non-fatal myocardial injury after noncardiac surgery, non-fatal stroke, and non-fatal cardiac arrest. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MINS not fulfilling the universal definition of myocardial infarction | 30 days after randomization | Number of patients who experience a myocardial injury after noncardiac surgery (MINS) not fulfilling the 3rd universal definition of myocardial infarction |
| Myocardial infarction | 30 days after randomization | Number of patients who experience a myocardial infarction |
| For patients in the blood pressure management arm: all-cause mortality | 30 days after randomization | Number of patients who die of any cause |
| A net risk-benefit outcome as a composite of vascular death, and non-fatal life-threatening,major or critical organ bleeding,MINS,stroke,peripheral arterial thrombosis,and symptomatic proximal venous thromboembolism | 30 days after randomization | Number of patients who have at least one of the following: vascular death, and non-fatal life-threatening, major or critical organ bleeding, myocardial injury after noncardiac surgery, stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism, |
| For patients in the blood pressure management arm: Myocardial infarction | 30 days after randomization | Number of patients who experience a myocardial infarction |
| For patients in the blood pressure management arm: MINS not fulfilling the universal definition of myocardial infarction | 30 days after randomization | Number of patients who experience MINS not fulfilling the universal definition of myocardial infarction |
| For patients in the blood pressure management arm: MINS | 30 days after randomization | Number of patients who experience a myocardial injury after noncardiac surgery (MINS) |
| BIMS | 30 days after randomization | Number of patients who experience bleeding independently associated with mortality after noncardiac surgery (BIMS) |
| MINS | 30 days after randomization | Number of patients who experience a myocardial injury after noncardiac surgery (MINS) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiac revascularization | 30 days after randomization | Number of patients who have undergo cardiac revascularization |
| Amputation | 30 days after randomization | Number of patients who have an amputation |
| Symptomatic pulmonary embolism | 30 days after randomization | Number of patients who experience a symptomatic pulmonary embolism |
| Symptomatic proximal DVT | 30 days after randomization | Number of patients who experience a symptomatic proximal DVT |
| Any symptomatic or asymptomatic proximal venous thromboembolism | 30 days after randomization | Number of patients who experience any (symptomatic or asymptomatic) proximal venous thromboembolism |
| Acute kidney injury | 30 days after randomization | Number of patients who experience an acute kidney injury |
| Re-hospitalization for vascular reasons | 30 days after randomization | Number of patients who experience a re-hospitalization for vascular reasons |
| Seizures | 30 days after randomization | Number of patients who experience a seizure |
| Infection/sepsis | 30 days after randomization | Number of patients who experience infection/sepsis |
| Disability | 30 days after randomization | Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule \[WHODAS 2.0\]). |
| Length of hospital stay | 30 days after randomization | Average length of hospital stay |
| Days alive and at home | 30 days after randomization | Number of days alive and at home |
| For patients in the blood pressure management arm: vascular death | 30 days after randomization | Number of patients who die from a vascular cause |
| For patients in the blood pressure management arm: non-fatal MINS | 30 days after randomization | Number of patients who experience a non-fatal MINS |
| For patients in the blood pressure management arm: non-fatal stroke | 30 days after randomization | Number of patients who experience a non-fatal stroke |
| For patients in the blood pressure management arm: non-fatal cardiac arrest | 30 days after randomization | Number of patients who experience non-fatal cardiac arrest |
| For patients in the blood pressure management arm: hemorrhagic stroke | 30 days after randomization | Number of patients who experience a hemorrhagic stroke |
| For patients in the blood pressure management arm: non-hemorrhagic stroke | 30 days after randomization | Number of patients who experience a non-hemorrhagic stroke |
| For patients in the blood pressure management arm: acute kidney injury | 30 days after randomization | Number of patients who experience an acute kidney injury |
| For patients in the blood pressure management arm: new renal replacement therapy | 30 days after randomization | Number of patients with new requirement for renal replacement therapy |
| For patients in the blood pressure management arm: acute congestive heart failure | 30 days after randomization | Number of patients who experience acute congestive heart failure |
| For patients in the blood pressure management arm: new clinically important atrial fibrillation | 30 days after randomization | Number of patients who experience new clinically important atrial fibrillation |
| For patients in the blood pressure management arm: sepsis | 30 days after randomization | Number of patients who experience a sepsis event |
| For patients in the blood pressure management arm: disability | 30 days after randomization | Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule \[WHODAS 2.0\]). |
| For patients in the blood pressure management arm: cancellation/postponement of surgery on the day of surgery due to BP concerns | 30 days after randomization | Number of patients whose surgery was cancelled/postponed on the day of surgery due to BP concerns |
| New renal replacement therapy | 30 days after randomization | Number of patients who require new renal replacement therapy |
| For patients in the blood pressure management arm: days alive and at home | 30 days after randomization | Number of days alive and at home |
| Myocardial infarction | 1 year after randomization | Number of patients who experience a myocardial infarction |
| Cardiac arrest | 1 year after randomization | Number of patients who experience cardiac arrest |
| For patients in the blood pressure management arm: all-cause mortality | 1 year after randomization | Number of patients who die of any cause |
| For patients in the blood pressure management arm: vascular mortality | 1 year after randomization | Number of patients who die of a vascular cause |
| For patients in the blood pressure management arm: myocardial infarction | 1 year after randomization | Number of patients who experience a myocardial infarction |
| For patients in the blood pressure management arm: cardiac arrest | 1 year after randomization | Number of patients who experience cardiac arrest |
| For patients in the blood pressure management arm: Disability | 1 year after randomization | Number of patients who experience disability (based on 12-item WHO Disability Assessment Schedule \[WHODAS 2.0\]). |
| For patients in the blood pressure management arm (CogPOISE-3 Sub study): Delirium | Post operative day one to three | Number of patients who experience delirium (based on 3D-CAM or ICU-CAM) |
| For patients in the blood pressure management arm (CogPOISE-3 Sub study): Cognitive decline | 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 |
| For patients in the blood pressure management arm: length of hospital stay | 30 days after randomization | Average length of hospital stay required |
| Life threatening bleeding | 30 days after randomization | Number of patients who experience a life threatening bleed. |
| Major bleeding | 30 days after randomization | Number of patients who experience a major bleed. |
| Critical organ bleeding | 30 days after randomization | Number of patients who experience bleeding in a critical organ. |
| International Society on Thrombosis and Haemostasis (ISTH) major bleeding | 30 days after randomization | Number of patients who experience an International Society on Thrombosis and Haemostasis (ISTH) major bleeding |
| Non-hemorrhagic stroke | 30 days after randomization | Number of patients who experience a non-hemorrhagic stroke |
| Peripheral arterial thrombosis | 30 days after randomization | Number of patients who experience peripheral arterial thrombosis |
| Symptomatic proximal venous thromboembolism | 30 days after randomization | Number of patients who experience a symptomatic proximal venous thromboembolism |
| All-cause mortality | 30 days after randomization | Number of patients who die of any cause |
| Vascular mortality | 30 days after randomization | Number of patients who die of vascular cause |
| Hemorrhagic stroke | 30 days after randomization | Number of patients who experience a hemorrhagic stroke |
| Transfusion rate | 30 days after randomization | Rate of transfusion in patients who experience a major bleeding event |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, China, Denmark, France, Germany, Hong Kong, India, Italy, Malaysia, Netherlands, New Zealand, Pakistan, Poland, Russia, South Africa, Spain, United Kingdom, United States
Outcome results
None listed