A Large, International, Placebo-controlled, Factorial Trial to Assess the Impact of Clonidine and Acetyl-salicylic Acid (ASA) in Patients Undergoing Noncardiac Surgery Who Are at Risk of a Perioperative Cardiovascular Event
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 10,010
- Locations
- 2
- Primary Endpoint
- All-cause Mortality and Nonfatal MI
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 45 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Active Clonidine and Active ASA
Intervention: Active Clonidine (Drug)
Active Clonidine and Active ASA
Intervention: Active ASA (Drug)
Active Clonidine and Placebo ASA
Intervention: Active Clonidine (Drug)
Active Clonidine and Placebo ASA
Intervention: Placebo ASA (Drug)
Placebo Clonidine and Active ASA
Intervention: Placebo Clonidine (Drug)
Placebo Clonidine and Active ASA
Intervention: Active ASA (Drug)
Placebo Clonidine and Placebo ASA
Intervention: Placebo Clonidine (Drug)
Placebo Clonidine and Placebo ASA
Intervention: Placebo ASA (Drug)
Outcomes
Primary Outcomes
All-cause Mortality and Nonfatal MI
Time Frame: 1 year
Composite of All-cause Mortality and Nonfatal MI
Time Frame: 30 days
Secondary Outcomes
- Composite Outcome by ASA Stratum(30 days)
- Composite of All-cause Mortality, Nonfatal MI, and Nonfatal Stroke(30 days)
- Safety Outcomes in Clonidine Trial(30 days)
- Individual Secondary Outcomes at 1 Year(1 year)
- Safety Outcomes in ASA Trial(30 days)
- Individual Secondary Outcomes(30 days)
- Composite Outcome at 1 Year(1 year)