Official Title: “PeriOperative ISchemic Evaluation-2 (POISE-2) Trial: A Pilot”

Major non-cardiac surgeries 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 low-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.

Study Type: Interventional

Study Design: Allocation: Randomized, Control: Placebo Control, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Study Primary Completion Date: December 2009

The POISE-2 Pilot Trial will provide the essential remaining feasibility data that POISE-2 researchers require prior to conducting a large international study to test the effect of ASA and Clonidine in preventing major vascular complications during the first 30 days after surgery.

The POISE-2 Pilot Trial is a factorial design randomized control trial that will compare ASA to placebo and clonidine to placebo. Patients in the POISE-2 pilot 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. Two to four hours prior to surgery, eligible patients are given ASA study drug and Clonidine study drug orally (162mg ASA or its placebo and 0.2mg Clonidine or its placebo) and a patch to apply (0.2mg/day Clonidine or its placebo). The patch will remain in place for 72 hours after surgery. After the surgery, patients ingest one tablet a day (81mg ASA or its placebo) 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. Troponin measurements will be collected between 6 to 12 hours after the operation and on the 1st, 2nd, and 3rd days after surgery. If blood tests reveal an elevation in the troponin measurement an electrocardiogram (ECG) will be undertaken immediately.

Research personnel will follow patients until 30 days after surgery.

Intervention(s) in this Clinical Trial

• Drug: active clonidine
  • Prior to surgery (goal 2-4 hours) patients will ingest 1 tablet of clonidine (0.2 mg) and will have a transdermal clonidine patch (0.2 mg/day) applied. The patch will be removed at 72 hours after surgery.
• Drug: active ASA
  • Prior to surgery (goal 2-4 hours) patients will ingest 2 ASA tablets (81 mg per tablet). After the first dose, patients will ingest 1 tablet daily for 7 or 30 days according to the stratum they are allocated to. Patients who are not able to take ASA orally will receive it rectally.
• Drug: Clonidine Placebo
  • Prior to surgery (goal 2-4 hours) patients will take oral clonidine placebo and will have a transdermal placebo patch applied. The patch will be removed at 72 hours after surgery.
• Drug: ASA Placebo
  • Prior to surgery (goal 2-4 hours) patients will ingest 2 ASA placebo tablets. After the first dose, patients will ingest 1 placebo tablet daily for 7 or 30 days according to the stratum they are allocated to. Patients who are not able to take placebo orally will receive it rectally.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: active clonidine and active ASA
• Experimental: active clonidine and ASA placebo
• Experimental: Clonidine placebo and active ASA
• Placebo Comparator: Clonidine placebo and ASA placebo

Primary Measures

• Feasibility of recruiting 90 patients in 6 months
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Feasibility of administering pre-operative ASA and clonidine
  • Time Frame: 6 months
    Safety Issue?: No
• Preliminary estimate of major bleeding and clinically significant hypotension
  • Time Frame: 30 days
    Safety Issue?: Yes
• Preliminary estimate of the composite of vascular death and non-fatal myocardial infarction.
  • Time Frame: 30 days
    Safety Issue?: Yes

Inclusion Criteria:

Patients undergoing noncardiac surgery who fulfill the following criteria:

• age ≥ 45 years
• expected to require at least an overnight hospital admission after noncardiac surgery, and fulfill any 1 of the following criteria:
• history of coronary artery disease
• peripheral vascular disease
• stroke
• undergoing major vascular surgery (i.e., vascular surgery except arteriovenous shunt, vein stripping procedures, and carotid endarterectomies)
• OR any 3 of 9 risk criteria:
• 1. undergoing major surgery [i.e., intraperitoneal, intrathoracic, or orthopedic surgery]
• 2. history of congestive heart failure
• 3. transient ischemic attack
• 4. diabetes and currently taking an oral hypoglycemic agent or insulin
• 5. age = or > than 70 years
• 6. hypertension
• 7. serum creatinine > 175 µmol/L
• 8. history of smoking within 2 years of surgery, or 9. undergoing emergent/urgent surgery

Exclusion Criteria:

• Patients has taken ASA < or = to 72 hours before scheduled surgery
• history of ASA or clonidine hypersensitivity or allergy
• systolic blood pressure < 105 mm Hg
• heart rate < 55 beats per minute
• second or third degree heart block without a pacemaker
• patient has active peptic ulcer disease
• Patient has had a bare metal stent in the six weeks prior to randomization
• Patient has had a drug eluting stent in the year prior to randomization
• Patient is currently taking an alpha-2 agonist, alpha methyldopa, reserpine, clopidogrel, or ticlopidine
• Patient undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
• Surgeon unwilling to have patient participate in a participate in a perioperative clonidine/ASA trial
• Prior enrolment in the POISE-2 pilot trial
• Unable to obtain or refusal to consent prior to surgery

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: McMaster University

Overall Clinical Trial Officials and Contacts

P. J. Devereaux, MD FRCP PHD Principal Investigator McMaster University  

Information obtained from ClinicalTrials.gov on September 07, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00860925

Study ID Number: POISE-2 01 2009

ClinicalTrials.gov Identifier: NCT00860925

Health Authority: Canada: Health Canada