POISE Trial: Perioperative Ischemic Evaluation Study (POISE)

• ClinicalTrials.gov Identifier: NCT00182039
• Recruitment Status: Terminated
• First Posted: September 16, 2005
• Last Update Posted: April 11, 2008
• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR); National Health and Medical Research Council, Australia; British Heart Foundation; AstraZeneca
• Information provided by: McMaster University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases	Drug: Metoprolol controlled release (CR); Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8351 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Perioperative Ischemic Evaluation Study (POISE) Trial
• Study Start Date: October 2002
• Actual Primary Completion Date: July 2007
• Actual Study Completion Date: August 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; metoprolol	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 Comparator: B; placebo	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.

Outcome Measures

Primary Outcome Measures :

1. major cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest) [ Time Frame: 30 days ]

Secondary Outcome Measures :

1. clinically significant atrial fibrillation rehospitalization for cardiac reasons [ Time Frame: 30 days and 1 year ]
2. nonfatal myocardial infarction [ Time Frame: 30 days and 1 year ]
3. nonfatal cardiac arrest [ Time Frame: 30 days and 1 year ]
4. cardiovascular death [ Time Frame: 30 days and 1 year ]
5. total mortality [ Time Frame: 30 days and 1 year ]
6. revascularization procedures (i.e. coronary artery bypass surgery and percutaneous transluminal coronary angioplasty) [ Time Frame: 30 days and 1 year ]
7. congestive heart failure [ Time Frame: 30 days and 1 year ]
8. clinically significant bradycardia [ Time Frame: 30 days ]
9. clinically significant hypotension [ Time Frame: 30 days ]
10. nonfatal stroke [ Time Frame: 30 days ]

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Canada, Ontario

McMaster University

Hamilton, Ontario, Canada, L8N 3Z5

Sponsors and Collaborators

Hamilton Health Sciences Corporation

Canadian Institutes of Health Research (CIHR)

National Health and Medical Research Council, Australia

British Heart Foundation

AstraZeneca

Investigators

• Principal Investigator: P.J. Devereaux, MD; McMaster University
• Principal Investigator: Homer Yang, MD; University of Ottawa

More Information

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. doi: 10.1016/j.ahj.2006.05.019.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Dr. P.J. Devereaux, McMaster University
• ClinicalTrials.gov Identifier: NCT00182039
• Other Study ID Numbers: MCT-50851-CT; ISRCTN17233551
• First Posted: September 16, 2005
• Last Update Posted: April 11, 2008
• Last Verified: January 2008

Keywords provided by McMaster University:

randomized controlled trial; blinded; noncardiac surgery; cardiovascular events

Additional relevant MeSH terms:

Cardiovascular Diseases; Metoprolol; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action