PeriOperative ISchemic Evaluation-2 Trial - Full Text View

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:

Drug Information available for: Aspirin Salicylic acid Clonidine Clonidine hydrochloride

U.S. FDA Resources

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.

Estimated Enrollment:	10000
Study Start Date:	July 2010
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2013 (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:

Are undergoing noncardiac surgery;
Are ≥ 45 years of age;
Are expected to require at least an overnight hospital admission after surgery; AND
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:

Consumption of ASA within 72 hours prior to surgery
Hypersensitivity or known allergy to ASA or clonidine
Systolic blood pressure < 105 mm Hg
Heart rate < 55 beats per minute in a patient who does not have a permanent pacemaker
Second or third degree heart block without a permanent pacemaker
Active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks
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
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
Drug-eluting coronary stent in the year prior to randomization
Bare-metal coronary stent in the 6 weeks prior to randomization
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;
Planned use - during the first 3 days after surgery - therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent
Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
Not consenting to participate in POISE-2 prior to surgery
Previously enrolled in POISE-2 Trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082874

Contacts

Contact: Andrea Robinson, BSc

+1-905-527-4322 ext 40473

poise2@phri.ca

Show 21 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

No publications provided

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:	December 3, 2012
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Australia: Department of Health and Ageing Therapeutic Goods Administration Austria: Ethikkommission Belgium: Federal Agency for Medicinal Products and Health Products Brazil: Ministry of Health Canada: Health Canada Chile: Instituto de Salud Publica 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: Ministry of Health Hong Kong: Department of Health India: Ministry of Health Italy: Ethics Committee Malaysia: Ministry of Health Pakistan: Ministry of Health Peru: Instituto Nacional de Salud South Africa: Medicines Control Council Spain: Spanish Agency of Medicines 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
Salicylates
Clonidine
Salicylic Acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents

Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists

ClinicalTrials.gov processed this record on May 16, 2013

PeriOperative ISchemic Evaluation-2 Trial (POISE-2)