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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01082874




Registration number
NCT01082874
Ethics application status
Date submitted
8/03/2010
Date registered
9/03/2010
Date last updated
25/08/2016

Titles & IDs
Public title
PeriOperative ISchemic Evaluation-2 Trial
Scientific 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
Secondary ID [1] 0 0
2009-018173-31
Secondary ID [2] 0 0
POISE-2 01MAR2010
Universal Trial Number (UTN)
Trial acronym
POISE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Active Clonidine
Treatment: Drugs - Placebo Clonidine
Treatment: Drugs - Active ASA
Treatment: Drugs - Placebo ASA

Experimental: Active Clonidine and Active ASA -

Experimental: Active Clonidine and Placebo ASA -

Experimental: Placebo Clonidine and Active ASA -

Placebo comparator: Placebo Clonidine and Placebo ASA -


Treatment: Drugs: 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.

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

Treatment: Drugs: 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

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of All-cause Mortality and Nonfatal MI
Timepoint [1] 0 0
30 days
Primary outcome [2] 0 0
All-cause Mortality and Nonfatal MI
Timepoint [2] 0 0
1 year
Secondary outcome [1] 0 0
Composite of All-cause Mortality, Nonfatal MI, and Nonfatal Stroke
Timepoint [1] 0 0
30 days
Secondary outcome [2] 0 0
Individual Secondary Outcomes
Timepoint [2] 0 0
30 days
Secondary outcome [3] 0 0
Composite Outcome by ASA Stratum
Timepoint [3] 0 0
30 days
Secondary outcome [4] 0 0
Safety Outcomes in ASA Trial
Timepoint [4] 0 0
30 days
Secondary outcome [5] 0 0
Safety Outcomes in Clonidine Trial
Timepoint [5] 0 0
30 days
Secondary outcome [6] 0 0
Composite Outcome at 1 Year
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Individual Secondary Outcomes at 1 Year
Timepoint [7] 0 0
1 year

Eligibility
Key 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
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2015
Sample size
Target
Accrual to date
Final
10010
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
National Coordination Office Australia and New Zealand - Parkville
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Ohio
Country [2] 0 0
Argentina
State/province [2] 0 0
Rosario
Country [3] 0 0
Austria
State/province [3] 0 0
Vienna
Country [4] 0 0
Belgium
State/province [4] 0 0
Brussels
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Chile
State/province [7] 0 0
Santiago
Country [8] 0 0
Colombia
State/province [8] 0 0
Bucamaranga
Country [9] 0 0
Denmark
State/province [9] 0 0
Herlev
Country [10] 0 0
France
State/province [10] 0 0
Boulogne-Billancourt
Country [11] 0 0
Germany
State/province [11] 0 0
Bonn
Country [12] 0 0
Hong Kong
State/province [12] 0 0
Hong Kong
Country [13] 0 0
India
State/province [13] 0 0
Bangalore
Country [14] 0 0
Italy
State/province [14] 0 0
Milan
Country [15] 0 0
Malaysia
State/province [15] 0 0
Kuala Lumpur
Country [16] 0 0
New Zealand
State/province [16] 0 0
Auckland
Country [17] 0 0
Pakistan
State/province [17] 0 0
Islamabad
Country [18] 0 0
Peru
State/province [18] 0 0
Lima
Country [19] 0 0
South Africa
State/province [19] 0 0
Durban
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Switzerland
State/province [21] 0 0
Basel
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Hull

Funding & Sponsors
Primary sponsor type
Other
Name
Hamilton Health Sciences Corporation
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
McMaster University
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01082874
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
P.J. Devereaux, MD, PhD
Address 0 0
Population Health Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01082874