PeriOperative ISchemic Evaluation-2 Trial (POISE-2)

Hamilton Health Sciences (HHS)

Status and phase: Completed; Phase 3

Conditions: Cardiovascular Disease

Treatments: Drug: Active Clonidine; Drug: Placebo ASA; Drug: Active ASA; Drug: Placebo Clonidine

Study type: Interventional

Funder types: Other

Identifiers

NCT01082874

POISE-2 01MAR2010

2009-018173-31 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10,010 patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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10,010 participants in 4 patient groups, including a placebo group

Active Clonidine and Active ASA

Experimental group

Treatment:

Drug: Active ASA

Drug: Active Clonidine

Active Clonidine and Placebo ASA

Experimental group

Treatment:

Drug: Placebo ASA

Drug: Active Clonidine

Placebo Clonidine and Active ASA

Experimental group

Treatment:

Drug: Placebo Clonidine

Drug: Active ASA

Placebo Clonidine and Placebo ASA

Placebo Comparator group

Treatment:

Drug: Placebo Clonidine

Drug: Placebo ASA