PeriOperative ISchemic Evaluation-2 Pilot

Condition(s) targeted: Cardiovascular Disease

Intervention: active clonidine (Drug); active ASA (Drug); Clonidine Placebo (Drug); ASA Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: McMaster University

Official(s) and/or principal investigator(s):
P. J. Devereaux, MD FRCP PHD, Principal Investigator, Affiliation: McMaster University

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.

Official title: PeriOperative ISchemic Evaluation-2 (POISE-2) Trial: A Pilot

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

Primary outcome: Feasibility of recruiting 90 patients in 6 months

Secondary outcome:

Feasibility of administering pre-operative ASA and clonidine

Preliminary estimate of major bleeding and clinically significant hypotension

Preliminary estimate of the composite of vascular death and non-fatal myocardial infarction.

Detailed description: 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.

Minimum age: 45 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Prince of Wales Hospital, Hong Kong, China

Walter C MacKenzie Health Sciences, Edmonton, Alberta T6G 2B7, Canada

Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada

St Joseph's Health Sciences, Hamilton, Ontario L8N 4A6, Canada

Starting date: May 2009
Last updated: March 8, 2010