PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Atherosclerotic Disease, Perioperative Bleeding

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Tranexamic Acid Placebo
* Drug: Rosuvastatin or matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: undergoing noncardiac surgery >45 years of age expected to require at least an overnight hospital admission after surgery; AND have a preoperative NT-pro-BNP measurement >100 ng/mL; OR 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: planned use of systemic Tranexamic Acid during surgery hypersensitivity or known allergy to TXA creatinine clearance <30 mL/min (MDRD) history of seizure disorder history of venous thromboembolism acute arterial thrombosis no preoperative measurement of hemoglobin subarachnoid hemorrhage within the past 30 days hematuria caused by diseases of the renal parenchyma previously enrolled in POISE-3 pilot trial 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: preoperative treatment with a statin or a non statin lipid lowering drug or ciclosporin during the 48 hours before surgery hypersensitivity or known allergy to Rosuvastatin pre-disposed factors for myopathy or rhabdomyolysis

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic Acid vs. matching placebo<br>Tranexamic Acid 1g bolus with anesthesia induction followed by 1g bolus at the start of surgical closure. | Drug: Tranexamic Acid<br> <br> * Other names: Cyklokapron;Drug: Tranexamic Acid Placebo<br> <br> |
| Experimental: Rosuvastatin vs. matching placebo<br>Rosuvastatin 20 mg orally or matching placebo once per day until 30 days after surgery | Drug: Rosuvastatin or matching placebo<br>* Subjects who are not on a statin will also be randomized to Rosuvastatin or Rosuvastatin placebo. 40mg preoperatively, followed by 20mg postoperatively (4-6 hours after surgical close) and 20mg/day for 30 days postoperatively.<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative intervention discontinuation | Interruption of the intervention longer than 24 hours within the first 10 days postoperatively, and longer than 48 hours from postoperative day 10 to 30. | Postoperative day 1 to 30. | 
| Change in hemoglobin | Change in preoperative hemoglobin to the morning hemoglobin recorded on day 1 after surgery. | Postoperative day 1. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | Postoperative day 30. | 
| Non-fatal myocardial infarction |  | Postoperative day 30. | 
| A composite of vascular mortality and non-fatal: myocardial infarction, stroke, cardiac arrest, pulmonary embolus, deep venous thrombosis, life threatening bleeding, major bleeding. | Event composite | Postoperative day 30. |