PeriOperative ISchemic Evaluation-2 Trial (POISE-2)

• ClinicalTrials.gov Identifier: NCT01082874
• Recruitment Status: Completed
• First Posted: March 9, 2010
• Results First Posted: August 25, 2016
• Last Update Posted: August 25, 2016
• Sponsor: Hamilton Health Sciences Corporation
• Collaborator: McMaster University
• Information provided by (Responsible Party): McMaster University ( Hamilton Health Sciences Corporation )

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Cardiovascular Disease	Drug: Active Clonidine; Drug: Placebo Clonidine; Drug: Active ASA; Drug: Placebo ASA	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10010 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: July 2010
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: January 2015

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Composite of All-cause Mortality and Nonfatal MI [ Time Frame: 30 days ]
2. All-cause Mortality and Nonfatal MI [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Composite of All-cause Mortality, Nonfatal MI, and Nonfatal Stroke [ Time Frame: 30 days ]
2. Individual Secondary Outcomes [ Time Frame: 30 days ]
   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.
3. Composite Outcome by ASA Stratum [ Time Frame: 30 days ]
   Composite outcome of all-cause mortality, nonfatal MI, cardiac revascularization procedure, nonfatal pulmonary emboli, and nonfatal deep venous thrombosis.
4. Safety Outcomes in ASA Trial [ Time Frame: 30 days ]
   Stroke, congestive heart failure, life-threatening bleeding, and major bleeding.
5. Safety Outcomes in Clonidine Trial [ Time Frame: 30 days ]
   Stroke, clinically important hypotension, clinically important bradycardia, and congestive heart failure.
6. Composite Outcome at 1 Year [ Time Frame: 1 year ]
   All-cause mortality, nonfatal MI, and nonfatal stroke.
7. Individual Secondary Outcomes at 1 Year [ Time Frame: 1 year ]
   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.

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:

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

Locations

United States, Ohio

National Coordination Office

Cleveland, Ohio, United States

Argentina

National Coordination Office

Rosario, Argentina

Australia, Victoria

National Coordination Office Australia and New Zealand

Parkville, Victoria, Australia

Austria

National Coordination Office

Vienna, Austria

Belgium

National Coordination Office

Brussels, Belgium

Brazil

National Coordination Office

Sao Paulo, Brazil

Canada, Ontario

National Coordination Office

Hamilton, Ontario, Canada

Chile

National Coordination Office

Santiago, Chile

Colombia

National Coordination Office

Bucamaranga, Colombia

Denmark

National Coordination Office

Herlev, Denmark

France

National Coordination Office

Boulogne-Billancourt, France

Germany

National Coordination Office

Bonn, Germany

Hong Kong

National Coordination Office

Hong Kong, Hong Kong

India

National Coordination Office

Bangalore, India

Italy

National Coordination Office

Milan, Italy

Malaysia

National Coordination Office

Kuala Lumpur, Malaysia

New Zealand

National Coordination Office

Auckland, New Zealand

Pakistan

National Coordination Office

Islamabad, Pakistan

Peru

National Coordination Office

Lima, Peru

South Africa

National Coordination Office

Durban, South Africa

Spain

National Coordination Office

Barcelona, Spain

Switzerland

National Coordination Office

Basel, Switzerland

United Kingdom

National Coordination Office

Hull, United Kingdom

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 of Results:

Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1494-503. doi: 10.1056/NEJMoa1401105. Epub 2014 Mar 31.

Devereaux PJ, Sessler DI, Leslie K, Kurz A, Mrkobrada M, Alonso-Coello P, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, Vanhelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1504-13. doi: 10.1056/NEJMoa1401106. Epub 2014 Mar 31.

Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh C, Mizera R, Jones PM, Tiboni M, Rodriguez RG, Popova E, Rojas Gomez MF, Meyhoff CS, Vanhelder T, Chan MT, Torres D, Parlow J, de Nadal Clanchet M, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov P, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Leslie K, Whitlock R, Devereaux PJ; POISE-2 Investigators. Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial. BMJ Open. 2014 Feb 25;4(2):e004886. doi: 10.1136/bmjopen-2014-004886.

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

Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Biccard BM, Sigamani A, Chan MTV, Sessler DI, Kurz A, Tittley JG, Rapanos T, Harlock J, Szalay D, Tiboni ME, Popova E, Vasquez SM, Kabon B, Amir M, Mrkobrada M, Mehra BR, El Beheiry H, Mata E, Tena B, Sabate S, Zainal Abidin MK, Shah VR, Balasubramanian K, Devereaux PJ. Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2). Br J Surg. 2018 Nov;105(12):1591-1597. doi: 10.1002/bjs.10925. Epub 2018 Jul 18.

Graham MM, Sessler DI, Parlow JL, Biccard BM, Guyatt G, Leslie K, Chan MTV, Meyhoff CS, Xavier D, Sigamani A, Kumar PA, Mrkobrada M, Cook DJ, Tandon V, Alvarez-Garcia J, Villar JC, Painter TW, Landoni G, Fleischmann E, Lamy A, Whitlock R, Le Manach Y, Aphang-Lam M, Cata JP, Gao P, Terblanche NCS, Ramana PV, Jamieson KA, Bessissow A, Mendoza GR, Ramirez S, Diemunsch PA, Yusuf S, Devereaux PJ. Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery. Ann Intern Med. 2018 Feb 20;168(4):237-244. doi: 10.7326/M17-2341. Epub 2017 Nov 14.

Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh CR, Mizera R, Jones PM, Tiboni M, Font A, Cegarra V, Gomez MF, Meyhoff CS, VanHelder T, Chan MT, Torres D, Parlow J, Clanchet Mde N, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov PS, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Wijeysundera DN, Leslie K, Forget P, Whitlock R, Yusuf S, Devereaux PJ; POISE-2 Investigators. Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial. JAMA. 2014 Dec 3;312(21):2254-64. doi: 10.1001/jama.2014.15284.

Devereaux PJ; POISE-2 Investigators. Rationale and design of the PeriOperative ISchemic Evaluation-2 (POISE-2) trial: an international 2 x 2 factorial randomized controlled trial of acetyl-salicylic acid vs. placebo and clonidine vs. placebo in patients undergoing noncardiac surgery. Am Heart J. 2014 Jun;167(6):804-9.e4. doi: 10.1016/j.ahj.2014.01.007. Epub 2014 Feb 22.

Chludzinski A, Irani C, Mascha EJ, Kurz A, Devereaux PJ, Sessler DI. Protocol understanding and anxiety in perioperative clinical trial patients approached for consent on the day of surgery. Mayo Clin Proc. 2013 May;88(5):446-54. doi: 10.1016/j.mayocp.2012.12.014.

• Responsible Party: Hamilton Health Sciences Corporation
• ClinicalTrials.gov Identifier: NCT01082874
• Other Study ID Numbers: POISE-2 01MAR2010; 2009-018173-31 ( EudraCT Number )
• First Posted: March 9, 2010
• Results First Posted: August 25, 2016
• Last Update Posted: August 25, 2016
• Last Verified: July 2016

Keywords provided by McMaster University ( Hamilton Health Sciences Corporation ):

Randomized Controlled Trial; Blinded; Clonidine; acetyl-salicylic acid (ASA); Perioperative vascular complications; Noncardiac surgery

Additional relevant MeSH terms:

Cardiovascular Diseases; Clonidine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents