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: Completed

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

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

National Coordination Office, Rosario, Argentina

National Coordination Office, Vienna, Austria

National Coordination Office, Brussels, Belgium

National Coordination Office, Sao Paulo, Brazil

National Coordination Office, Santiago, Chile

National Coordination Office, Bucamaranga, Colombia

National Coordination Office, Herlev, Denmark

National Coordination Office, Boulogne-Billancourt, France

National Coordination Office, Bonn, Germany

National Coordination Office, Hong Kong, Hong Kong

National Coordination Office, Bangalore, India

National Coordination Office, Milan, Italy

National Coordination Office, Kuala Lumpur, Malaysia

National Coordination Office, Auckland, New Zealand

National Coordination Office, Islamabad, Pakistan

National Coordination Office, Lima, Peru

National Coordination Office, Durban, South Africa

National Coordination Office, Barcelona, Spain

National Coordination Office, Basel, Switzerland

National Coordination Office, Hull, United Kingdom

National Coordination Office, Cleveland, Ohio, United States

National Coordination Office, Hamilton, Ontario, Canada

National Coordination Office Australia and New Zealand, Parkville, Victoria, Australia

Related publications:

Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh C, Mizera R, Jones PM, Tiboni M, Rodriguez RG, Popova E, Rojas Gomez MF, Meyhoff CS, Vanhelder T, Chan MT, Torres D, Parlow J, de Nadal Clanchet M, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov P, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Leslie K, Whitlock R, Devereaux PJ; POISE-2 Investigators. Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial. BMJ Open. 2014 Feb 25;4(2):e004886. doi: 10.1136/bmjopen-2014-004886.

Starting date: July 2010
Last updated: April 7, 2015