EPIC (Evaluating Perioperative Ischemia Reduction by Clonidine)

The EPIC (Evaluating Perioperative Ischemia Reduction by Clonidine) Study: A Randomized, Double-blinded Trial of Clonidine for Reducing Cardiac Morbidity and Mortality Following Non-cardiac Surgery.

In Canada 1 patient in 200 dies within 30 days of an operation. More than half of these deaths are the direct result of a heart related complication. This cause of death happens 4 times more often than in the same people who do not have an operation. We do not have an effective way to stop these heart attacks. Stress causes the heart rate and the blood pressure to go up which causes the heart to work harder and may be the reason for some heart attacks. One group of drugs that stops the heart from working harder and decrease the number of heart related complications are BETA-BLOCKERS. We wish to add another drug, which has been shown to reduce heart rate and blood pressure, will reduce the number of heart attacks after an operation. CLONIDINE has been shown to reduce heart attacks after operations. Since we know it is not a good idea to stop beta-blockers we want to see if giving clonidine as well as a beta-blocker is safe and has the desired effect of decreasing the number of heart attacks. We want to find out how good the combination of these two drugs are at decreasing the number of heart attacks.

Hypothesis: The addition of clonidine to chronic b-blockade will reduce mortality and cardiac morbidity among intermediate-to-high risk patients undergoing non-cardiac surgery.

Study Overview

• Status: Unknown
• Conditions: Heart Disease
• Intervention / Treatment: Drug: clonidine hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 165
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 45 years
2. Current use of b-blocker therapy>=30 days prior to surgery
3. Undergoing non-cardiac surgery with an expected length of stay ≥ 48 hours for medical reasons
4. Informed consent
5. Undergoing major vascular surgery (excluding carotid endarterectomy, dialysis shunt, and vein stripping) OR

Meet >= 2of the following criteria:

1. Coronary artery disease
2. Congestive heart failure
3. Stroke or transient ischemic attack
4. Diabetes mellitus requiring oral hypoglycemic or insulin therapy
5. Preoperative renal insufficiency (creatinine clearance below 60 mL/min)
6. Peripheral vascular disease, as defined by any of the following: history of ischemic intermittent claudication or rest pain, history of revascularization procedure to legs, peripheral arterial obstruction of >= 50% luminal diameter
7. Age >=70 years
8. Intermediate-risk surgical procedure: intra-peritoneal, intra-thoracic, carotid endarterectomy, major orthopedic (hip, knee, spine) surgery, radical prostatectomy, or head-and-neck surgery

Exclusion criteria: - if meets any of the following

1. Prior adverse reaction to clonidine or a-2 agonists
2. Current use of Clonidine or a-2 agonists
3. Current congestive heart failure
4. Only b-blocker taken by patient is sotalol
5. Left ventricular ejection fraction <=40%
6. Systolic blood pressure < = 90 mmHg
7. Concomitant life-threatening disease likely to limit life expectancy to <=30 days.
8. Clinically significant aortic stenosis, defined as an aortic valve area <=1.0 cm2 and/or peak trans-valvular pressure gradient >= 25 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To preform feasibility study looking at the safety and efficacy of adding clonidine to chronic b-blockade on patient-relevant outcomes (mortality, myocardial infarction, prolonged hospitalization) in large randomized controlled trials	Daily until discharge and 30 days after surgery

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Canadian Anesthesiologists' Society
• Investigators: Principal Investigator: Duminda Wijeysundera, MD, Toronto General Hospital, University Health Network

Publications and helpful links

General Publications

• Wijeysundera DN, Choi PT, Badner NH, Brasher PM, Dresser GK, Delgado DH, Beattie WS. A randomized feasibility trial of clonidine to reduce perioperative cardiac risk in patients on chronic beta-blockade: the EPIC study. Can J Anaesth. 2014 Nov;61(11):995-1003. doi: 10.1007/s12630-014-0226-6. Epub 2014 Sep 5.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: June 8, 2006
• First Submitted That Met QC Criteria: June 8, 2006
• First Posted (Estimate): June 12, 2006

Study Record Updates

• Last Update Posted (Estimate): October 9, 2009
• Last Update Submitted That Met QC Criteria: October 8, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: alpha 2 agonists; cardiac events; non cardiac surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Heart Diseases; Ischemia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: REB#05-0146-B