PeriOperative ISchemic Evaluation-2 Trial

Phase 3

Completed

Interventions: Drug: Placebo Clonidine
Drug: Active Clonidine
Drug: Placebo ASA
Drug: Active ASA

Brief Summary: Major surgeries not involving the heart are common, and major heart problems during or after such surgeries represent a large population health problem. Few treatments to prevent heart problems around the time of surgery have been tested. There is encouraging data suggesting that small doses of Acetyl-Salicylic Acid (ASA) and Clonidine, which are two medications, given individually for a short period before and after major surgeries may prevent major heart problems. The POISE-2 Trial is a large international study to test if ASA and Clonidine can prevent heart attacks and deaths from heart problems around the time of surgery.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo Clonidine and Placebo ASA	Placebo Clonidine	-
Placebo Clonidine and Placebo ASA	Placebo ASA	-
Placebo Clonidine and Active ASA	Placebo Clonidine	-
Active Clonidine and Placebo ASA	Active Clonidine	-
Placebo Clonidine and Active ASA	Active ASA	-
Active Clonidine and Active ASA	Active Clonidine	-
Active Clonidine and Placebo ASA	Placebo ASA	-
Active Clonidine and Active ASA	Active ASA	-

Primary Outcome Measures

Name	Time	Method
All-cause Mortality and Nonfatal MI	1 year
Composite of All-cause Mortality and Nonfatal MI	30 days

Secondary Outcome Measures

Name	Time	Method
Composite Outcome by ASA Stratum	30 days	Composite outcome of all-cause mortality, nonfatal MI, cardiac revascularization procedure, nonfatal pulmonary emboli, and nonfatal deep venous thrombosis.
Composite of All-cause Mortality, Nonfatal MI, and Nonfatal Stroke	30 days
Safety Outcomes in Clonidine Trial	30 days	Stroke, clinically important hypotension, clinically important bradycardia, and congestive heart failure.
Individual Secondary Outcomes at 1 Year	1 year	All cause mortality, vascular mortality, MI, nonfatal cardiac arrest, cardiac revascularization procedure, stroke, pulmonary emboli, deep venous thrombosis, amputation, peripheral arterial thrombosis, new diagnosis of cancer, diagnosis of recurrent cancer and rehospitalization for vascular reason.
Safety Outcomes in ASA Trial	30 days	Stroke, congestive heart failure, life-threatening bleeding, and major bleeding.
Individual Secondary Outcomes	30 days	All-cause mortality, vascular mortality, MI, nonfatal cardiac arrest, cardiac revascularization procedure, pulmonary emboli, deep venous thrombosis, clinically important atrial fibrillation, amputation, peripheral arterial thrombosis, infection/sepsis, rehospitalization for vascular reasons, length of hospital stay, length of intensive care unit / cardiac care unit (ICU/CCU) stay, and new acute renal failure requiring dialysis.
Composite Outcome at 1 Year	1 year	All-cause mortality, nonfatal MI, and nonfatal stroke.

Locations (2): National Coordination Office
🇬🇧
Hull, United Kingdom
National Coordination Office Australia and New Zealand
🇦🇺
Parkville, Victoria, Australia