Clinical trial NCT02546648: PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study
Official title: PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study (POISE-3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerotic Disease
Perioperative Bleeding
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
name: Hamilton Health Sciences Corporation
First posted: 2015-09-11
Enrollment: 100
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Postoperative intervention discontinuation
timeFrame: Postoperative day 1 to 30.
measure: Change in hemoglobin
timeFrame: Postoperative day 1.
Secondary outcomes:
measure: All-cause mortality
timeFrame: Postoperative day 30.
measure: Non-fatal myocardial infarction
timeFrame: Postoperative day 30.
measure: A composite of vascular mortality and non-fatal: myocardial infarction, stroke, cardiac arrest, pulmonary embolus, deep venous thrombosis, life threatening bleeding, major bleeding.
timeFrame: Postoperative day 30.
Other outcomes:
measure: Safety Outcomes for Rosuvastatin assessed by Statin induced myopathy
timeFrame: Postoperative day 30.
measure: Safety Outcomes for Tranexamic Acid assessed by Seizure, pulmonary emboli, deep venous thrombosis, vascular mortality
timeFrame: Postoperative day 30.
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: James Khan, MD
role: STUDY_CHAIR
References:
citation: Marcucci M, Duceppe E, Le Manach Y, Kearon C, Eikelboom JW, Pohl K, Vincent J, Darvish-Kazem S, Srinathan SK, Neary JDD, Parlow JL, Kurz A, Gross PL, Mrkobrada M, Balasubramanian K, Sessler DI, Devereaux PJ. Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial. Pilot Feasibility Stud. 2020 Jul 21;6:104. doi: 10.1186/s40814-020-00643-9. eCollection 2020.