PeriOperative ISchemic Evaluation-2 Trial
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Intervention: Active Clonidine; Placebo Clonidine; Active ASA; Placebo ASA
Intervention description: 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.; Pre-op (goal 2-4 hours): 2 oral placebo tablets and transdermal placebo patch. Patch to be removed 72 hours post-op.; 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; Pre-op (goal 2-4 hours): 2 oral placebo tablets. Post-op: patients ingest one placebo tablet a day 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
Intervention MeSH terms: Clonidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10010.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Randomized Controlled Trial; Blinded; Clonidine; acetyl-salicylic acid (ASA); Perioperative vascular complications; Noncardiac surgery

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.
    

Eligibility criteria:

        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