Atherosclerotic Disease, Perioperative Bleeding
Conditions
Brief summary
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
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.
Interventions
DRUGTranexamic Acid
DRUGTranexamic Acid Placebo
DRUGRosuvastatin or matching placebo
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.
Sponsors
Population Health Research Institute
Hamilton Health Sciences Corporation
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative intervention discontinuation | Postoperative day 1 to 30. | 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. |
| Change in hemoglobin | Postoperative day 1. | Change in preoperative hemoglobin to the morning hemoglobin recorded on day 1 after surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A composite of vascular mortality and non-fatal: myocardial infarction, stroke, cardiac arrest, pulmonary embolus, deep venous thrombosis, life threatening bleeding, major bleeding. | Postoperative day 30. | Event composite |
| All-cause mortality | Postoperative day 30. | — |
| Non-fatal myocardial infarction | Postoperative day 30. | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcomes for Tranexamic Acid assessed by Seizure, pulmonary emboli, deep venous thrombosis, vascular mortality | Postoperative day 30. | myocardial infarction, stroke, non-fatal cardiac arrest, and cardiac revascularization procedure. |
| Safety Outcomes for Rosuvastatin assessed by Statin induced myopathy | Postoperative day 30. | — |
Countries
Canada
Outcome results
None listed