Cardiovascular Disease
Conditions
Keywords
Randomized Controlled Trial, Blinded, Clonidine, acetyl-salicylic acid (ASA), Perioperative vascular complications, Noncardiac surgery
Brief summary
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.
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.
Interventions
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.
DRUGASA 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.
DRUGactive 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.
DRUGactive 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.
Sponsors
The Physicians' Services Incorporated Foundation
Canadian Network and Centre for Trials Internationally
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of recruiting 90 patients in 6 months | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Feasibility of administering pre-operative ASA and clonidine | 6 months |
| Preliminary estimate of major bleeding and clinically significant hypotension | 30 days |
| Preliminary estimate of the composite of vascular death and non-fatal myocardial infarction. | 30 days |
Countries
Canada, China
Outcome results
None listed