PeriOperative ISchemic Evaluation-3 Trial (POISE-3)

Population Health Research Institute (PHRI)

Status and phase: Completed; Phase 3

Conditions: Perioperative Bleeding; Arterial Thrombosis; Venous Thrombosis

Treatments: Other: Perioperative hypertension-avoidance strategy; Other: Perioperative hypotension-avoidance strategy; Drug: Tranexamic Acid; Drug: Placebo (Saline)

Study type: Interventional

Funder types: Other

Identifiers

NCT03505723

2018.02.08

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9,535 patients

Sex: All

Ages: 45+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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9,535 participants in 4 patient groups, including a placebo group

Tranexamic Acid (TXA)

Active Comparator group

Description:

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).

Treatment:

Drug: Tranexamic Acid

Placebo (0.9% normal saline)

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo (Saline)

Hypotension-avoidance strategy

Active Comparator group

Description:

Aims to avoid hypotension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative).

Treatment:

Other: Perioperative hypotension-avoidance strategy

Perioperative hypertension-avoidance strategy

Placebo Comparator group

Description:

Aims to avoid hypertension before surgery (preoperative), during surgery (intraoperative) and for the first 2 days after the day of surgery (postoperative).

Treatment:

Other: Perioperative hypertension-avoidance strategy