PeriOperative ISchemic Evaluation-2 Trial

POISE-2 is a multicentre, international, blinded, 2x2 factorial randomized controlled trial of acetyl-salicylic acid (ASA) and clonidine. The primary objective is to determine the impact of clonidine versus placebo and ASA versus placebo on the 30-day risk of all-cause mortality or nonfatal myocardial infarction in patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery. Patients in the POISE-2 trial will be randomly assigned to one of four groups: ASA and Clonidine together, ASA and Clonidine placebo, ASA placebo and Clonidine, or a ASA placebo and Clonidine placebo. Research personnel will follow patients at 30 days post-randomization and 1 year post-randomization.

Inclusion criteria

• Are undergoing noncardiac surgery;
• Are ≥ 45 years of age;
• Are expected to require at least an overnight hospital admission after surgery; AND
• Fulfill one or more of the following 5 criteria:

• History of coronary artery disease
• History of peripheral vascular disease
• History of stroke
• Undergoing major vascular surgery
• Any 3 of the following 9 criteria:

• undergoing major surgery (i.e. intraperitoneal, intrathoracic, retroperitoneal or major orthopedic surgery
• history of congestive heart failure
• transient ischemic attack
• diabetes and currently taking an oral hypoglycemic agent or insulin
• age ≥ 70 years
• hypertension
• serum creatinine > 175 µmol/L (> 2.0 mg/dL)
• history of smoking within 2 years of surgery
• undergoing urgent/emergent surgery

Exclusion criteria

• Consumption of ASA within 72 hours prior to surgery
• Hypersensitivity or known allergy to ASA or clonidine
• Systolic blood pressure < 105 mm Hg
• Heart rate < 55 beats per minute in a patient who does not have a permanent pacemaker
• Second or third degree heart block without a permanent pacemaker
• Active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks
• Intracranial hemorrhage documented by neuro-imaging, in the 6 months prior to randomization. This does not include petechial hemorrhagic transformation of a primary ischemic stroke
• Subarachnoid hemorrhage or epidural hematoma unless the event occurred more than 6 months prior to randomization and the offending aneurysm or arterial lesion has been repaired
• Drug-eluting coronary stent in the year prior to randomization
• Bare-metal coronary stent in the 6 weeks prior to randomization
• Thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel) or ticagrelor within 72 hours prior to surgery; or intent to restart a thienopyridine or ticagrelor during the first 7 days post-op; or currently taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors or reserpine;
• Planned use - during the first 3 days after surgery - therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent
• Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
• Not consenting to participate in POISE-2 prior to surgery
• Previously enrolled in POISE-2 Trial