Official Title: “Perioperative Ischemic Evaluation Study (POISE) Trial”

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

Study Type: Interventional

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

Study Primary Completion Date: July 2007

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.

Intervention(s) in this Clinical Trial

• Drug: Metoprolol controlled release (CR)
  • Patients received the first dose of the study drug (i.e., oral metoprolol CR or matching placebo 100 mg) 2-4 hours prior to surgery. Administration of the study drug at each dosing time required a patient to have a heart rate ≥ 50 beats per minute (bpm) and a systolic blood pressure (SBP) ≥ 100 mmHg. If the patient's heart rate was ≥ 80 bpm and their SBP ≥ 100 mmHg at any time during the first 6 hours after surgery, the patient received their first postoperative dose (i.e., 100 mg of the study drug) orally. Patients who did not receive the study drug during the first 6 hours after surgery received 100 mg of the study drug orally at 6 hours after surgery. Twelve hours after the first postoperative dose patients started taking oral metoprolol CR or placebo 200 mg daily for 30 days.
• Drug: Placebo
  • Patients received the first dose of the study drug (i.e., oral metoprolol CR or matching placebo 100 mg) 2-4 hours prior to surgery. Administration of the study drug at each dosing time required a patient to have a heart rate ≥ 50 beats per minute (bpm) and a systolic blood pressure (SBP) ≥ 100 mmHg. If the patient's heart rate was ≥ 80 bpm and their SBP ≥ 100 mmHg at any time during the first 6 hours after surgery, the patient received their first postoperative dose (i.e., 100 mg of the study drug) orally. Patients who did not receive the study drug during the first 6 hours after surgery received 100 mg of the study drug orally at 6 hours after surgery. Twelve hours after the first postoperative dose patients started taking oral metoprolol CR or placebo 200 mg daily for 30 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • metoprolol
• Placebo Comparator: B
  • placebo

Primary Measures

• major cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest)
  • Time Frame: 30 days
    Safety Issue?: No

Secondary Measures

• clinically significant atrial fibrillation rehospitalization for cardiac reasons
  • Time Frame: 30 days and 1 year
    Safety Issue?: No
• nonfatal myocardial infarction
  • Time Frame: 30 days and 1 year
    Safety Issue?: No
• nonfatal cardiac arrest
  • Time Frame: 30 days and 1 year
    Safety Issue?: No
• cardiovascular death
  • Time Frame: 30 days and 1 year
    Safety Issue?: Yes
• total mortality
  • Time Frame: 30 days and 1 year
    Safety Issue?: Yes
• revascularization procedures (i.e. coronary artery bypass surgery and percutaneous transluminal coronary angioplasty)
  • Time Frame: 30 days and 1 year
    Safety Issue?: No
• congestive heart failure
  • Time Frame: 30 days and 1 year
    Safety Issue?: Yes
• clinically significant bradycardia
  • Time Frame: 30 days
    Safety Issue?: Yes
• clinically significant hypotension
  • Time Frame: 30 days
    Safety Issue?: Yes
• nonfatal stroke
  • Time Frame: 30 days
    Safety Issue?: Yes

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

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 Principal Investigator McMaster University  

Information obtained from ClinicalTrials.gov on December 03, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00182039

Study ID Number: MCT-50851-CT

ClinicalTrials.gov Identifier: NCT00182039

Health Authority: Canada: Health Canada