Clinical trial NCT00182039: POISE Trial: Perioperative Ischemic Evaluation Study
Official title: Perioperative Ischemic Evaluation Study (POISE) Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Keywords: randomized controlled trial
blinded
noncardiac surgery
cardiovascular events
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: National Health and Medical Research Council, Australia
name: British Heart Foundation
name: AstraZeneca
First posted: 2005-09-16
Enrollment: 8351
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This trial will evaluate the ability of metoprolol (a beta-blocker drug) to prevent heart attacks and deaths around the time of surgery.

Detailed description: The POISE Trial is a large multi-centre, blinded, randomized controlled group trial of metoprolol vs placebo in 10,000 at risk patients undergoing noncardiac surgery. The POISE Trial will determine the impact of perioperative administration of metoprolol on cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest) during the 30 day post-operative period in at risk patients undergoing noncardiac surgery.

Assuming a control group event rate of 6% for our primary outcome, we determined randomization of 8000 patients would provide 85% power and 10,000 patients 92% power to detect a relative risk reduction of 25% (two-sided alpha = 0.05). We set a goal to randomize 10,000 patients recognizing that we would have adequate power if we randomized 8000 patients. Without knowledge of the trial results and knowing that we had randomized more than 8000 patients and had a higher than predicted event rate, the Operations Committee decided to terminate recruitment on July 31, 2007 primarily because the remaining study drug expired in September 2007.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing noncardiac surgery
* ≥ 45 years of age; either sex.
* Have an expected length of stay ≥ 24 hours
* Fulfill any one of the following 6 criteria:

  * coronary artery disease;
  * peripheral vascular disease;
  * history of stroke due to atherothrombotic disease;
  * hospitalization for congestive heart failure within 3 years of randomization;
  * undergoing major vascular surgery; OR
  * any 3 of the following 7 criteria: scheduled for high risk surgery (i.e. intraperitoneal or intrathoracic); emergency/urgent surgery; any history of congestive heart failure; history of a transient ischemic attack (TIA); diabetes and currently on an oral hypoglycemic agent or insulin therapy; preoperative serum creatinine \> 175 µmol/L (\> 2.0 mg/dl); or age \> 70 years.

Exclusion Criteria:

* Contraindication to metoprolol including any of the following: significant bradycardia (heart rate \< 50 beats per minute); second or third degree heart block without a pacemaker; asthma that has been active within the last decade; and history of chronic obstructive pulmonary disease (COPD) with bronchospasm on pulmonary function tests.
* Clinical plan to use a beta-blocker preoperatively or during the first 30 postoperative days
* Prior adverse reaction to a beta-blocker
* Coronary artery bypass graft (CABG) surgery with complete revascularization in the preceding 5 years and no evidence of cardiac ischemia since the CABG surgery
* Patients undergoing low risk surgical procedures (potential examples include transurethral procedures \[transurethral prostatectomies (TURPs), stone baskets, etc.\], ophthalmologic procedures under topical or regional anesthesia \[cornea transplants, cataract surgery, etc.\], and surgeries with limited physiological stresses \[digital re-implantation, nerve repairs, etc.\] )
* Concurrent use of verapamil
* Prior enrollment in this trial

Primary outcomes:
measure: major cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest)
timeFrame: 30 days
Secondary outcomes:
measure: clinically significant atrial fibrillation rehospitalization for cardiac reasons
timeFrame: 30 days and 1 year
measure: nonfatal myocardial infarction
timeFrame: 30 days and 1 year
measure: nonfatal cardiac arrest
timeFrame: 30 days and 1 year
measure: cardiovascular death
timeFrame: 30 days and 1 year
measure: total mortality
timeFrame: 30 days and 1 year
measure: revascularization procedures (i.e. coronary artery bypass surgery and percutaneous transluminal coronary angioplasty)
timeFrame: 30 days and 1 year
measure: congestive heart failure
timeFrame: 30 days and 1 year
measure: clinically significant bradycardia
timeFrame: 30 days
measure: clinically significant hypotension
timeFrame: 30 days
measure: nonfatal stroke
timeFrame: 30 days
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: P.J. Devereaux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ottawa
name: Homer Yang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: POISE Trial Investigators; Devereaux PJ, Yang H, Guyatt GH, Leslie K, Villar JC, Monteri VM, Choi P, Giles JW, Yusuf S. Rationale, design, and organization of the PeriOperative ISchemic Evaluation (POISE) trial: a randomized controlled trial of metoprolol versus placebo in patients undergoing noncardiac surgery. Am Heart J. 2006 Aug;152(2):223-30. doi: 10.1016/j.ahj.2006.05.019.
citation: Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S; POISE (PeriOperative ISchemic Evaluation) Investigators. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011 Apr 19;154(8):523-8. doi: 10.7326/0003-4819-154-8-201104190-00003.
citation: POISE Study Group; Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Malaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. doi: 10.1016/S0140-6736(08)60601-7. Epub 2008 May 12.