PeriOperative ISchemic Evaluation-2 Trial (POISE-2)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
McMaster University
Information provided by (Responsible Party):
McMaster University ( Hamilton Health Sciences Corporation )
ClinicalTrials.gov Identifier:
NCT01082874
First received: March 8, 2010
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

Major surgeries not involving the heart are common, and major heart problems during or after such surgeries represent a large population health problem. Few treatments to prevent heart problems around the time of surgery have been tested. There is encouraging data suggesting that small doses of Acetyl-Salicylic Acid (ASA) and Clonidine, which are two medications, given individually for a short period before and after major surgeries may prevent major heart problems. The POISE-2 Trial is a large international study to test if ASA and Clonidine can prevent heart attacks and deaths from heart problems around the time of surgery.


Condition Intervention Phase
Cardiovascular Disease
Drug: Active Clonidine
Drug: Placebo Clonidine
Drug: Active ASA
Drug: Placebo ASA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Large, International, Placebo-controlled, Factorial Trial to Assess the Impact of Clonidine and Acetyl-salicylic Acid (ASA) in Patients Undergoing Noncardiac Surgery Who Are at Risk of a Perioperative Cardiovascular Event

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Composite of all-cause mortality and nonfatal MI [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • All-cause mortality and nonfatal MI [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Composite of all-cause mortality, nonfatal MI, and nonfatal stroke [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Individual secondary outcomes [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    All-cause mortality, vascular mortality, MI, nonfatal cardiac arrest, cardiac revascularization procedure, pulmonary emboli, deep venous thrombosis, clinically important atrial fibrillation, amputation, peripheral arterial thrombosis, infection/sepsis, rehospitalization for vascular reasons, length of hospital stay, length of intensive care unit / cardiac care unit (ICU/CCU) stay, and new acute renal failure requiring dialysis.

  • Composite outcome by ASA stratum [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Composite outcome of all-cause mortality, nonfatal MI, cardiac revascularization procedure, nonfatal pulmonary emboli, and nonfatal deep venous thrombosis.

  • Safety outcomes in ASA trial [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Stroke, congestive heart failure, life-threatening bleeding, and major bleeding.

  • Safety outcomes in clonidine trial [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Stroke, clinically important hypotension, clinically important bradycardia, and congestive heart failure.

  • Composite outcome at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    All-cause mortality, nonfatal MI, and nonfatal stroke.

  • Individual secondary outcomes at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    All cause mortality, vascular mortality, MI, nonfatal cardiac arrest, cardiac revascularization procedure, stroke, pulmonary emboli, deep venous thrombosis, amputation, peripheral arterial thrombosis, new diagnosis of cancer, diagnosis of recurrent cancer and rehospitalization for vascular reason.


Enrollment: 10010
Study Start Date: July 2010
Estimated Study Completion Date: January 2015
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active Clonidine and Active ASA Drug: Active Clonidine
Pre-op (goal 2-4 hours): 2 x 0.1mg oral tablets and transdermal patch (0.2 mg/day). Patch to be removed 72 hours post-op.
Other Name: CATAPRES, CATAPRES-TTS
Drug: Active ASA
Pre-op (goal 2-4 hours): 2 x 100mg oral tablets. Post-op: patients ingest one tablet a day (100 mg ASA) for 7 days if patient was were taking ASA chronically prior to surgery or for 30 days if they were not chronically taking ASA prior to surgery
Other Name: ASPIRIN
Experimental: Active Clonidine and Placebo ASA Drug: Active Clonidine
Pre-op (goal 2-4 hours): 2 x 0.1mg oral tablets and transdermal patch (0.2 mg/day). Patch to be removed 72 hours post-op.
Other Name: CATAPRES, CATAPRES-TTS
Drug: Placebo ASA
Pre-op (goal 2-4 hours): 2 oral placebo tablets. Post-op: patients ingest one placebo tablet a day for 7 days if patient was were taking ASA chronically prior to surgery or for 30 days if they were not chronically taking ASA prior to surgery
Experimental: Placebo Clonidine and Active ASA Drug: Placebo Clonidine
Pre-op (goal 2-4 hours): 2 oral placebo tablets and transdermal placebo patch. Patch to be removed 72 hours post-op.
Drug: Active ASA
Pre-op (goal 2-4 hours): 2 x 100mg oral tablets. Post-op: patients ingest one tablet a day (100 mg ASA) for 7 days if patient was were taking ASA chronically prior to surgery or for 30 days if they were not chronically taking ASA prior to surgery
Other Name: ASPIRIN
Placebo Comparator: Placebo Clonidine and Placebo ASA Drug: Placebo Clonidine
Pre-op (goal 2-4 hours): 2 oral placebo tablets and transdermal placebo patch. Patch to be removed 72 hours post-op.
Drug: Placebo ASA
Pre-op (goal 2-4 hours): 2 oral placebo tablets. Post-op: patients ingest one placebo tablet a day for 7 days if patient was were taking ASA chronically prior to surgery or for 30 days if they were not chronically taking ASA prior to surgery

Detailed Description:

POISE-2 is a multicentre, international, blinded, 2x2 factorial randomized controlled trial of acetyl-salicylic acid (ASA) and clonidine. The primary objective is to determine the impact of clonidine versus placebo and ASA versus placebo on the 30-day risk of all-cause mortality or nonfatal myocardial infarction in patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery. Patients in the POISE-2 trial will be randomly assigned to one of four groups: ASA and Clonidine together, ASA and Clonidine placebo, ASA placebo and Clonidine, or a ASA placebo and Clonidine placebo. Research personnel will follow patients at 30 days post-randomization and 1 year post-randomization.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Are undergoing noncardiac surgery;
  2. Are ≥ 45 years of age;
  3. Are expected to require at least an overnight hospital admission after surgery; AND
  4. Fulfill one or more of the following 5 criteria:

    • History of coronary artery disease
    • History of peripheral vascular disease
    • History of stroke
    • Undergoing major vascular surgery
    • Any 3 of the following 9 criteria:

      • undergoing major surgery (i.e. intraperitoneal, intrathoracic, retroperitoneal or major orthopedic surgery
      • history of congestive heart failure
      • transient ischemic attack
      • diabetes and currently taking an oral hypoglycemic agent or insulin
      • age ≥ 70 years
      • hypertension
      • serum creatinine > 175 µmol/L (> 2.0 mg/dL)
      • history of smoking within 2 years of surgery
      • undergoing urgent/emergent surgery

Exclusion Criteria:

  1. Consumption of ASA within 72 hours prior to surgery
  2. Hypersensitivity or known allergy to ASA or clonidine
  3. Systolic blood pressure < 105 mm Hg
  4. Heart rate < 55 beats per minute in a patient who does not have a permanent pacemaker
  5. Second or third degree heart block without a permanent pacemaker
  6. Active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks
  7. Intracranial hemorrhage documented by neuro-imaging, in the 6 months prior to randomization. This does not include petechial hemorrhagic transformation of a primary ischemic stroke
  8. Subarachnoid hemorrhage or epidural hematoma unless the event occurred more than 6 months prior to randomization and the offending aneurysm or arterial lesion has been repaired
  9. Drug-eluting coronary stent in the year prior to randomization
  10. Bare-metal coronary stent in the 6 weeks prior to randomization
  11. Thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel) or ticagrelor within 72 hours prior to surgery; or intent to restart a thienopyridine or ticagrelor during the first 7 days post-op; or currently taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors or reserpine;
  12. Planned use - during the first 3 days after surgery - therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent
  13. Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
  14. Not consenting to participate in POISE-2 prior to surgery
  15. Previously enrolled in POISE-2 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: NCT01082874

  Show 23 Study Locations
Sponsors and Collaborators
Hamilton Health Sciences Corporation
McMaster University
Investigators
Principal Investigator: P.J. Devereaux, MD, PhD Population Health Research Institute
Study Chair: Salim Yusuf, DPhil Population Health Research Institute
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: McMaster University ( Hamilton Health Sciences Corporation )
ClinicalTrials.gov Identifier: NCT01082874     History of Changes
Other Study ID Numbers: POISE-2 01MAR2010, 2009-018173-31
Study First Received: March 8, 2010
Last Updated: September 22, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
India: Ministry of Health
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
New Zealand: Medsafe
Pakistan: Ministry of Health
Peru: Instituto Nacional de Salud
South Africa: Medicines Control Council
Spain: Ministerio de Sanidad, Servicios Sociales e Igualdad
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by McMaster University:
Randomized Controlled Trial
Blinded
Clonidine
acetyl-salicylic acid (ASA)
Perioperative vascular complications
Noncardiac surgery

Additional relevant MeSH terms:
Cardiovascular Diseases
Aspirin
Clonidine
Salicylic Acid
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Analgesics
Analgesics, Non-Narcotic
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antifungal Agents
Antihypertensive Agents
Antipyretics
Antirheumatic Agents
Autonomic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Dermatologic Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Keratolytic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 29, 2014