POISE Trial: Perioperative Ischemic Evaluation Study

Condition(s) targeted: Cardiovascular Diseases

Intervention: Metoprolol controlled release (CR) (Drug); Placebo (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Hamilton Health Sciences

Official(s) and/or principal investigator(s):
P.J. Devereaux, MD, Principal Investigator, Affiliation: Hamilton Health Sciences
Homer Yang, MD, Principal Investigator, Affiliation: University of Ottawa

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

Official title: Perioperative Ischemic Evaluation Study (POISE) Trial

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: major cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest)

Secondary outcome:

clinically significant atrial fibrillation rehospitalization for cardiac reasons

nonfatal myocardial infarction

nonfatal cardiac arrest

cardiovascular death

total mortality

revascularization procedures (i.e. coronary artery bypass surgery and percutaneous transluminal coronary angioplasty)

congestive heart failure

clinically significant bradycardia

clinically significant hypotension

nonfatal stroke

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.

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

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

McMaster University, Hamilton, Ontario L8N 3Z5, Canada

Related publications:

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.

Starting date: October 2002
Ending date: August 2007
Last updated: April 10, 2008