PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study (POISE-3)

McMaster University

Status and phase: Completed; Phase 3

Conditions: Atherosclerotic Disease; Perioperative Bleeding

Treatments: Drug: Rosuvastatin or matching placebo; Drug: Tranexamic Acid Placebo; Drug: Tranexamic Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT02546648

POISE3034

Details and patient eligibility

About

A placebo-controlled, factorial trial to assess the impact of rosuvastatin and tranexamic acid (TXA) in patients undergoing noncardiac surgery who are at risk of a perioperative cardiovascular event.

Full description

The POISE-3 pilot is a randomized controlled trial of 100 patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery. Utilizing a partial factorial design, the POISE-3 pilot will determine the effect of rosuvastatin versus placebo and TXA versus placebo in the perioperative setting.

Enrollment: 100 patients

Sex: All

Ages: 45+ years old

Volunteers: No 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; AND

4. have a preoperative NT-pro-BNP measurement >100 ng/mL; OR

5. if a preoperative NT-pro-BNP measurement is not available, then the patient must fulfill 1 or more of the following 5 criteria:

   • history of coronary artery disease

   • history of peripheral vascular disease

   • history of stroke

   • undergoing major vascular surgery

   • have any 3 of the following 9 risk criteria:

     • undergoing major surgery
     • history of congestive heart failure
     • history of a transient ischemic attack
     • diabetic and currently taking an oral hypoglycemic agent or insulin
     • age >70 years
     • hypertension
     • serum creatinine > 175 umol/L (>2.0 mg/dl)
     • history of smoking within 2 years of surgery
     • undergoing emergent/urgent surgery

Exclusion criteria

1. planned use of systemic Tranexamic Acid during surgery
2. hypersensitivity or known allergy to TXA
3. creatinine clearance <30 mL/min (MDRD)
4. history of seizure disorder
5. history of venous thromboembolism
6. acute arterial thrombosis
7. no preoperative measurement of hemoglobin
8. subarachnoid hemorrhage within the past 30 days
9. hematuria caused by diseases of the renal parenchyma
10. previously enrolled in POISE-3 pilot trial
11. not consenting to participate in POISE-3 pilot trial prior to surgery

Patients meeting any of the following criteria will be excluded from the Rosuvastatin/Placebo arm:

1. preoperative treatment with a statin or a non statin lipid lowering drug or ciclosporin during the 48 hours before surgery
2. hypersensitivity or known allergy to Rosuvastatin
3. pre-disposed factors for myopathy or rhabdomyolysis

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups

Tranexamic Acid vs. matching placebo

Experimental group

Description:

Tranexamic Acid 1g bolus with anesthesia induction followed by 1g bolus at the start of surgical closure.

Treatment:

Drug: Tranexamic Acid

Drug: Tranexamic Acid Placebo

Rosuvastatin vs. matching placebo

Experimental group

Description:

Rosuvastatin 20 mg orally or matching placebo once per day until 30 days after surgery

Treatment:

Drug: Rosuvastatin or matching placebo