POISE Trial: Perioperative Ischemic Evaluation Study

Cardiovascular Diseases Clinical Trial

— POISE  

Official title:

Perioperative Ischemic Evaluation Study (POISE) Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00182039
• Other study ID #: MCT-50851-CT
• Secondary ID: ISRCTN17233551
• Status: Terminated
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: April 10, 2008
• Start date: October 2002
• Est. completion date: August 2007

Study information

• Verified date: January 2008
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8351
• Est. completion date: August 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	McMaster University	Hamilton	Ontario

Sponsors (5)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	AstraZeneca, British Heart Foundation, Canadian Institutes of Health Research (CIHR), National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	major cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest)		30 days	No
Secondary	clinically significant atrial fibrillation rehospitalization for cardiac reasons		30 days and 1 year	No
Secondary	nonfatal myocardial infarction		30 days and 1 year	No
Secondary	nonfatal cardiac arrest		30 days and 1 year	No
Secondary	cardiovascular death		30 days and 1 year	Yes
Secondary	total mortality		30 days and 1 year	Yes
Secondary	revascularization procedures (i.e. coronary artery bypass surgery and percutaneous transluminal coronary angioplasty)		30 days and 1 year	No
Secondary	congestive heart failure		30 days and 1 year	Yes
Secondary	clinically significant bradycardia		30 days	Yes
Secondary	clinically significant hypotension		30 days	Yes
Secondary	nonfatal stroke		30 days	Yes