POISE Trial: Perioperative Ischemic Evaluation Study - Full Text View

Sponsor:	Hamilton Health Sciences
Collaborators:	Canadian Institutes of Health Research (CIHR) National Health and Medical Research Council, Australia British Heart Foundation AstraZeneca
Information provided by:	McMaster University
ClinicalTrials.gov Identifier:	NCT00182039

Purpose

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

Condition	Intervention	Phase
Cardiovascular Diseases	Drug: Metoprolol controlled release (CR) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Perioperative Ischemic Evaluation Study (POISE) Trial

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Surgery

Drug Information available for: Metoprolol Metoprolol Tartrate Metoprolol succinate Metoprolol fumarate

U.S. FDA Resources

Further study details as provided by McMaster University:

Primary Outcome Measures:

major cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest) [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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

Enrollment:	8351
Study Start Date:	October 2002
Study Completion Date:	August 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental 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.
B: Placebo Comparator 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.

Arms

Assigned Interventions

A: Experimental

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.

B: Placebo Comparator

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.

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

Ages Eligible for Study:	45 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182039

Locations

Canada, Ontario
McMaster University
Hamilton, Ontario, Canada, L8N 3Z5

Sponsors and Collaborators

Hamilton Health Sciences

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.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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, Málaga 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. Epub 2008 May 12.

Responsible Party:	McMaster University ( Dr. P.J. Devereaux )
Study ID Numbers:	MCT-50851-CT, ISRCTN17233551
Study First Received:	September 9, 2005
Last Updated:	April 10, 2008
ClinicalTrials.gov Identifier:	NCT00182039 History of Changes
Health Authority:	Canada: Health Canada

Keywords provided by McMaster University:

randomized controlled trial
blinded
noncardiac surgery
cardiovascular events

Additional relevant MeSH terms:

Sympatholytics
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cardiovascular Agents
Antihypertensive Agents
Metoprolol
Pharmacologic Actions

Autonomic Agents
Metoprolol succinate
Therapeutic Uses
Adrenergic beta-Antagonists
Cardiovascular Diseases
Adrenergic Antagonists
Peripheral Nervous System Agents
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on February 08, 2010