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POISE Trial: Perioperative Ischemic Evaluation Study

This study has been terminated.
(Please see detailed description for reason why study was terminated.)
Sponsor:
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
First received: September 9, 2005
Last updated: April 10, 2008
Last verified: January 2008
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Perioperative Ischemic Evaluation Study (POISE) Trial

Resource links provided by NLM:


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
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.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. P.J. Devereaux, McMaster University
ClinicalTrials.gov Identifier: NCT00182039     History of Changes
Other Study ID Numbers: MCT-50851-CT, ISRCTN17233551
Study First Received: September 9, 2005
Last Updated: April 10, 2008
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
randomized controlled trial
blinded
noncardiac surgery
cardiovascular events

Additional relevant MeSH terms:
Cardiovascular Diseases
Metoprolol
Metoprolol succinate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympatholytics
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014