PeriOperative ISchemic Evaluation-2 Trial

NCT01082874 | Completed Phase 3 Results DMC

• 2 other identifiers: POISE-2 01MAR20102009-018173-31
• Study Type: interventional
• Target: 10,010
• Locations: 22 countries
• Sites: 22

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.

Conditions

Cardiovascular Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Composite of All-cause Mortality and Nonfatal MI

  30 days

• All-cause Mortality and Nonfatal MI

  1 year

Secondary Outcomes (7)

• Composite of All-cause Mortality, Nonfatal MI, and Nonfatal Stroke

  30 days

• Individual Secondary Outcomes

  30 days

• Composite Outcome by ASA Stratum

  30 days

• Safety Outcomes in ASA Trial

  30 days

• Safety Outcomes in Clonidine Trial

  30 days

Study Arms (4)

Active Clonidine and Active ASA

EXPERIMENTAL

Drug: Active Clonidine; Drug: Active ASA

Active Clonidine and Placebo ASA

EXPERIMENTAL

Drug: Active Clonidine; Drug: Placebo ASA

Placebo Clonidine and Active ASA

EXPERIMENTAL

Drug: Placebo Clonidine; Drug: Active ASA

Placebo Clonidine and Placebo ASA

PLACEBO COMPARATOR

Drug: Placebo Clonidine; Drug: Placebo ASA

Interventions

Active Clonidine DRUG

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.

Also known as: CATAPRES, CATAPRES-TTS

Active Clonidine and Active ASA; Active Clonidine and Placebo ASA

Placebo Clonidine DRUG

Pre-op (goal 2-4 hours): 2 oral placebo tablets and transdermal placebo patch. Patch to be removed 72 hours post-op.

Placebo Clonidine and Active ASA; Placebo Clonidine and Placebo ASA

Active ASA DRUG

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

Also known as: ASPIRIN

Active Clonidine and Active ASA; Placebo Clonidine and Active ASA

Placebo ASA DRUG

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

Active Clonidine and Placebo ASA; Placebo Clonidine and Placebo ASA

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• McMaster University: collaborator

Study Sites (23)

National Coordination Office

Cleveland, Ohio, United States

Location

National Coordination Office

Rosario, Argentina

Location

National Coordination Office Australia and New Zealand

Parkville, Victoria, Australia

Location

National Coordination Office

Vienna, Austria

Location

National Coordination Office

Brussels, Belgium

Location

National Coordination Office

São Paulo, Brazil

Location

National Coordination Office

Hamilton, Ontario, Canada

Location

National Coordination Office

Santiago, Chile

Location

National Coordination Office

Bucamaranga, Colombia

Location

National Coordination Office

Herlev, Denmark

Location

National Coordination Office

Boulogne-Billancourt, France

Location

National Coordination Office

Bonn, Germany

Location

National Coordination Office

Hong Kong, Hong Kong

Location

National Coordination Office

Bangalore, India

Location

National Coordination Office

Milan, Italy

Location

National Coordination Office

Kuala Lumpur, Malaysia

Location

National Coordination Office

Auckland, New Zealand

Location

National Coordination Office

Islamabad, Pakistan

Location

National Coordination Office

Lima, Peru

Location

National Coordination Office

Durban, South Africa

Location

National Coordination Office

Barcelona, Spain

Location

National Coordination Office

Basel, Switzerland

Location

National Coordination Office

Hull, United Kingdom

Location

Related Publications (11)

• 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.

  PMID: 24679062 RESULT

• 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.

  PMID: 24679061 RESULT

• 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.

  PMID: 24568963 RESULT

• Roshanov PS, Walsh MW, Garg AX, Cuerden M, Lam NN, Hildebrand AM, Lee VW, Mrkobrada M, Leslie K, Chan MTV, Borges FK, Wang CY, Xavier D, Sessler DI, Szczeklik W, Meyhoff CS, Srinathan SK, Sigamani A, Villar JC, Chow CK, Polanczyk CA, Patel A, Harrison TG, Fielding-Singh V, Cata JP, Parlow J, de Nadal M, Devereaux PJ. Preoperative estimated glomerular filtration rate to predict cardiac events in major noncardiac surgery: a secondary analysis of two large international studies. Br J Anaesth. 2025 Feb;134(2):297-307. doi: 10.1016/j.bja.2024.10.039. Epub 2025 Jan 2.

  PMID: 39753401 DERIVED

• Turan A, Rivas E, Devereaux PJ, Pu X, Rodriguez-Patarroyo FA, Yalcin EK, Nault R, Maheshwari K, Ruetzler K, Sessler DI. Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial. Eur J Anaesthesiol. 2023 May 1;40(5):365-371. doi: 10.1097/EJA.0000000000001816. Epub 2023 Mar 9.

  PMID: 36891761 DERIVED

• 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.

  PMID: 35224730 DERIVED

• 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.

  PMID: 30019751 DERIVED

• 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.

  PMID: 29132159 DERIVED

• 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.

  PMID: 25399007 DERIVED

• 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.

  PMID: 24890528 DERIVED

• 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.

  PMID: 23639498 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Clonidine; Aspirin

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: P.J. Devereaux, MD, PhD, FRCPC
• Organization: Population Health Research Institute

philipj@mcmaster.ca

905-527-4322

Study Officials

• P.J. Devereaux, MD, PhD

  Population Health Research Institute

  PRINCIPAL INVESTIGATOR

• Salim Yusuf, DPhil

  Population Health Research Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 9, 2010
• Study Start: July 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: January 1, 2015
• Last Updated: August 25, 2016
• Results First Posted: August 25, 2016

Record last verified: 2016-07

Locations

DE (1); BR (1); MY (1); ZA (1); US (1); CO (1); BE (1); CH (1); NZ (1); GB (1); AR (1); DK (1); PE (1); HK (1); AU (1); CL (1); IN (1); FR (1); ES (1); CA (1); IT (1); PA (1)