POISE2-pilot: PeriOperative ISchemic Evaluation-2 Pilot

Sponsor

McMaster University (Other)

Overall Status

Completed

CT.gov ID

NCT00860925

Collaborator

The Physicians' Services Incorporated Foundation (Other), Canadian Network and Centre for Trials Internationally (Other)

Enrollment

Locations

Arms

Duration (Months)

22.5

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Drug: active clonidine Drug: active ASA Drug: Clonidine Placebo Drug: ASA Placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

May 1, 2009

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: active clonidine and active ASA	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. Other Names: CATAPRES, CATAPRES TTS 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. Other Names: ENTROPHEN CHEWABLE
Experimental: active clonidine and ASA placebo	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. Other Names: CATAPRES, CATAPRES TTS 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. Other Names: ENTROPHEN CHEWABLE placebo
Experimental: Clonidine placebo and active ASA	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. Other Names: ENTROPHEN CHEWABLE 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. Other Names: CATAPRES placebo and CATAPRES TTS placebo
Placebo Comparator: Clonidine placebo and ASA placebo	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. Other Names: CATAPRES placebo and CATAPRES TTS placebo 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. Other Names: ENTROPHEN CHEWABLE placebo

Outcome Measures

Primary Outcome Measures

Feasibility of recruiting 90 patients in 6 months [6 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

undergoing major surgery [i.e., intraperitoneal, intrathoracic, or orthopedic surgery]
history of congestive heart failure
transient ischemic attack
diabetes and currently taking an oral hypoglycemic agent or insulin
age = or > than 70 years
hypertension
serum creatinine > 175 µmol/L
history of smoking within 2 years of surgery, or
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Walter C MacKenzie Health Sciences	Edmonton	Alberta	Canada	T6G 2B7
2	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
3	St Joseph's Health Sciences	Hamilton	Ontario	Canada	L8N 4A6
4	Prince of Wales Hospital	Hong Kong		China