PeriOperative ISchemic Evaluation-3 Trial

Population Health Research Institute9,535 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

9,535

Conditions

Perioperative Bleeding Venous Thrombosis Arterial Thrombosis

Interventions

Tranexamic AcidDRUG

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.

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.

Perioperative hypotension-avoidance strategyOTHER

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.

Eligibility

Sex: ALLMin age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (114)

Outcomes

Primary Outcomes

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