PeriOperative ISchemic Evaluation-2 Trial

Condition(s) targeted: Cardiovascular Disease

Intervention: Active Clonidine (Drug); Placebo Clonidine (Drug); Active ASA (Drug); Placebo ASA (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Hamilton Health Sciences Corporation

Official(s) and/or principal investigator(s):
P.J. Devereaux, MD, PhD, Principal Investigator, Affiliation: Population Health Research Institute
Salim Yusuf, DPhil, Study Chair, Affiliation: Population Health Research Institute

Overall contact:
Andrea Robinson, BSc, Phone: +1-905-527-4322, Ext: 40473, Email: poise2@phri.ca

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.

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

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

Primary outcome:

Composite of all-cause mortality and nonfatal MI

All-cause mortality and nonfatal MI

Secondary outcome:

Composite of all-cause mortality, nonfatal MI, and nonfatal stroke

Individual secondary outcomes

Composite outcome by ASA stratum

Safety outcomes in ASA trial

Safety outcomes in clonidine trial

Composite outcome at 1 year

Individual secondary outcomes at 1 year

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.

Minimum age: 45 Years. Maximum age: N/A. Gender(s): Both.

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

Andrea Robinson, BSc, Phone: +1-905-527-4322, Ext: 40473, Email: poise2@phri.ca

National Coordination Office, Rosario, Argentina; Not yet recruiting

National Coordination Office, Vienna, Austria; Recruiting

National Coordination Office, Brussels, Belgium; Recruiting

National Coordination Office, Sao Paulo, Brazil; Recruiting

National Coordination Office, Santiago, Chile; Recruiting

National Coordination Office, Bucamaranga, Colombia; Recruiting

National Coordination Office, Herlev, Denmark; Recruiting

National Coordination Office, Boulogne-Billancourt, France; Recruiting

National Coordination Office, Hong Kong, Hong Kong; Recruiting

National Coordination Office, Bangalore, India; Recruiting

National Coordination Office, Milan, Italy; Recruiting

National Coordination Office, Kuala Lumpur, Malaysia; Recruiting

National Coordination Office, Islamabad, Pakistan; Recruiting

National Coordination Office, Lima, Peru; Recruiting

National Coordination Office, Durban, South Africa; Recruiting

National Coordination Office, Barcelona, Spain; Recruiting

National Coordination Office, Basel, Switzerland; Recruiting

National Coordination Office, Hull, United Kingdom; Recruiting

National Coordination Office, Cleveland, Ohio, United States; Recruiting

National Coordination Office, Hamilton, Ontario, Canada; Recruiting

National Coordination Office, Parkville, Victoria, Australia; Recruiting

Starting date: July 2010
Last updated: December 3, 2012