PeriOperative ISchemic Evaluation-2 Trial

Hamilton Health Sciences Corporation10,010 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

10,010

Conditions

Cardiovascular Disease

Interventions

Active ClonidineDRUG

Pre-op (goal 2-4 hours): 2 x 0.1mg oral tablets and transdermal patch (0.2 mg/day). Patch to be removed 72 hours post-op.

Placebo ClonidineDRUG

Pre-op (goal 2-4 hours): 2 oral placebo tablets and transdermal placebo patch. Patch to be removed 72 hours post-op.

Active ASADRUG

Pre-op (goal 2-4 hours): 2 x 100mg oral tablets. Post-op: patients ingest one tablet a day (100 mg ASA) for 7 days if patient was were taking ASA chronically prior to surgery or for 30 days if they were not chronically taking ASA prior to surgery

Eligibility

Sex: ALLMin age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Are undergoing noncardiac surgery; 2. Are ≥ 45 years of age; 3. Are expected to require at least an overnight hospital admission after surgery; AND 4. 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: 1. Consumption of ASA within 72 hours prior to surgery 2. Hypersensitivity or known allergy to ASA or clonidine 3. Systolic blood pressure \< 105 mm Hg 4. Heart rate \< 55 beats per minute in a patient who does not have a permanent pacemaker 5. Second or third degree heart block without a permanent pacemaker 6. Active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks 7. 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 8. 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 9. Drug-eluting coronary stent in the year prior to randomization 10. Bare-metal coronary stent in the 6 weeks prior to randomization 11. 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; 12. Planned use - during the first 3 days after surgery - therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent 13. Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery 14. Not consenting to participate in POISE-2 prior to surgery 15. Previously enrolled in POISE-2 Trial

Locations (23)

National Coordination Office

Cleveland, Ohio, United States

National Coordination Office

Rosario, Argentina

Outcomes

Primary Outcomes

Composite of All-cause Mortality and Nonfatal MI

Time frame: 30 days

All-cause Mortality and Nonfatal MI

Time frame: 1 year

Secondary Outcomes

Composite of All-cause Mortality, Nonfatal MI, and Nonfatal Stroke

Time frame: 30 days

Individual Secondary Outcomes

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.

Time frame: 30 days

Composite Outcome by ASA Stratum

Composite outcome of all-cause mortality, nonfatal MI, cardiac revascularization procedure, nonfatal pulmonary emboli, and nonfatal deep venous thrombosis.

Time frame: 30 days

Safety Outcomes in ASA Trial

Stroke, congestive heart failure, life-threatening bleeding, and major bleeding.

Time frame: 30 days

Safety Outcomes in Clonidine Trial

Stroke, clinically important hypotension, clinically important bradycardia, and congestive heart failure.

Time frame: 30 days

Composite Outcome at 1 Year

All-cause mortality, nonfatal MI, and nonfatal stroke.

Data from ClinicalTrials.gov

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