PeriOperative ISchemic Evaluation-2 Trial

Cardiovascular Disease Clinical Trial

— POISE-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01082874
• Other study ID #: POISE-2 01MAR2010
• Secondary ID: 2009-018173-31
• Status: Completed
• Phase: Phase 3
• First received: March 8, 2010
• Last updated: April 7, 2015
• Start date: July 2010
• Est. completion date: January 2015

Study information

• Verified date: April 2015
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaChile: Instituto de Salud Pública de ChileColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHong Kong: Department of HealthIndia: Ministry of HealthItaly: The Italian Medicines AgencyMalaysia: Ministry of HealthNew Zealand: MedsafePakistan: Ministry of HealthPeru: Instituto Nacional de SaludSouth Africa: Medicines Control CouncilSpain: Ministerio de Sanidad, Servicios Sociales e IgualdadSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10010
• Est. completion date: January 2015
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

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

Locations

Country	Name	City	State
Argentina	National Coordination Office	Rosario
Australia	National Coordination Office Australia and New Zealand	Parkville	Victoria
Austria	National Coordination Office	Vienna
Belgium	National Coordination Office	Brussels
Brazil	National Coordination Office	Sao Paulo
Canada	National Coordination Office	Hamilton	Ontario
Chile	National Coordination Office	Santiago
Colombia	National Coordination Office	Bucamaranga
Denmark	National Coordination Office	Herlev
France	National Coordination Office	Boulogne-Billancourt
Germany	National Coordination Office	Bonn
Hong Kong	National Coordination Office	Hong Kong
India	National Coordination Office	Bangalore
Italy	National Coordination Office	Milan
Malaysia	National Coordination Office	Kuala Lumpur
New Zealand	National Coordination Office	Auckland
Pakistan	National Coordination Office	Islamabad
Peru	National Coordination Office	Lima
South Africa	National Coordination Office	Durban
Spain	National Coordination Office	Barcelona
Switzerland	National Coordination Office	Basel
United Kingdom	National Coordination Office	Hull
United States	National Coordination Office	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	McMaster University

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Denmark,  France,  Germany,  Hong Kong,  India,  Italy,  Malaysia,  New Zealand,  Pakistan,  Peru,  South Africa,  Spain,  Switzerland,  United Kingdom, 

References & Publications (3)

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, — View Citation

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, — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of all-cause mortality and nonfatal MI		30 days	No
Primary	All-cause mortality and nonfatal MI		1 year	No
Secondary	Composite of all-cause mortality, nonfatal MI, and nonfatal stroke		30 days	No
Secondary	Individual secondary outcomes	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.	30 days	No
Secondary	Composite outcome by ASA stratum	Composite outcome of all-cause mortality, nonfatal MI, cardiac revascularization procedure, nonfatal pulmonary emboli, and nonfatal deep venous thrombosis.	30 days	No
Secondary	Safety outcomes in ASA trial	Stroke, congestive heart failure, life-threatening bleeding, and major bleeding.	30 days	Yes
Secondary	Safety outcomes in clonidine trial	Stroke, clinically important hypotension, clinically important bradycardia, and congestive heart failure.	30 days	Yes
Secondary	Composite outcome at 1 year	All-cause mortality, nonfatal MI, and nonfatal stroke.	1 year	No
Secondary	Individual secondary outcomes at 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.	1 year	No