Official Title: “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”

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.

Study Type: Interventional

Study Design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Study Primary Completion Date: July 2013

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 MI 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.

Intervention(s) in this Clinical Trial

• Drug: Active Clonidine
  • 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.
• Drug: Placebo Clonidine
  • Pre-op (goal 2-4 hours): 2 oral placebo tablets and transdermal placebo patch. Patch to be removed 72 hours post-op.
• Drug: Active ASA
  • 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
• Drug: Placebo ASA
  • 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Active Clonidine and Active ASA
• Experimental: Active Clonidine and Placebo ASA
• Experimental: Placebo Clonidine and Active ASA
• Placebo Comparator: Placebo Clonidine and Placebo ASA

Primary Measures

• Composite of all-cause mortality and nonfatal MI
  • Time Frame: 30 days
    Safety Issue?: No
• All-cause mortality and nonfatal MI
  • Time Frame: 1 year
    Safety Issue?: No

Secondary Measures

• Composite of all-cause mortality, nonfatal MI, and nonfatal stroke
  • Time Frame: 30 days
    Safety Issue?: No
• Individual secondary outcomes
  • Time Frame: 30 days
    Safety Issue?: No
• Composite outcome by ASA stratum
  • Time Frame: 30 days
    Safety Issue?: No
• Safety outcomes in ASA trial
  • Time Frame: 30 days
    Safety Issue?: Yes
• Safety outcomes in clonidine trial
  • Time Frame: 30 days
    Safety Issue?: Yes
• Composite outcome at 1 year
  • Time Frame: 1 year
    Safety Issue?: No
• Individual secondary outcomes at 1 year
  • Time Frame: 1 year
    Safety Issue?: No

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, 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. Currently taking an alpha-2 agonist, alpha methyldopa, reserpine, ticagrelor, or thienopyridine
• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Hamilton Health Sciences

Overall Clinical Trial Officials and Contacts

P.J. Devereaux, MD, PhD Principal Investigator Population Health Research Institute  

Overall Contact: Andrea Robinson, BSc +1-905-527-4322 poise2@phri.ca

Information obtained from ClinicalTrials.gov on September 07, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01082874

Study ID Number: POISE-2 01MAR2010

ClinicalTrials.gov Identifier: NCT01082874

Health Authority: Australia: National Health and Medical Research Council