title: A randomized feasibility trial of clonidine to reduce perioperative cardiac risk in patients on chronic beta-blockade: the EPIC study.
abstract: OBJECTIVE
  Clonidine may help prevent cardiac complications in patients undergoing non-cardiac surgery and receiving chronic beta-blocker therapy. We conducted a multicentre pilot randomized trial to estimate recruitment rates for a full-scale trial and to assess the safety and tolerability of combining clonidine with chronic beta-blockade.
  
  
  METHODS
  Patients who were at elevated perioperative cardiac risk, receiving chronic beta-blockade, and scheduled for major non-cardiac surgery were recruited in a blinded (participants, clinicians, outcome assessors) placebo-controlled randomized trial at three Canadian hospitals. Participants were randomized to clonidine (0.2 mg oral tablet one hour before surgery, plus 0.2 mg·day(-1) transdermal patch placed one hour before surgery and removed four days after surgery or hospital discharge, whichever came first) or matching placebo. Feasibility was evaluated based on recruitment rates, with each centre being required to recruit 50 participants within 12-18 months. Additionally, we reviewed study drug withdrawals and safety outcomes, including clinically significant hypotension or bradycardia.
  
  
  RESULTS
  Eighty-two of the 168 participants were randomized to receive clonidine and 86 to receive placebo. The average time to recruit 50 participants at each centre was 14.3 months. Six patients (7%) withdrew from clonidine, while four (5%) withdrew from placebo. Based on qualitative review, there were no major safety concerns related to clonidine. There was a moderate overall rate of cardiac morbidity, with 18 participants (11%) suffering postoperative myocardial infarction.
  
  
  CONCLUSIONS
  This pilot randomized trial confirmed the feasibility, safety, and tolerability of a full-scale trial of oral and transdermal clonidine for reducing the risk of cardiac complications during non-cardiac surgery. This trial was registered at www.clinicaltrials.gov: NCT00335582.
authors.affiliation: Department of Anesthesia, Toronto General Hospital and University of Toronto, Eaton Wing 3-450, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada, d.wijeysundera@utoronto.ca.
authors.forename: Duminda N
authors.initials: DN
authors.lastname: Wijeysundera
authors.forename: Peter T
authors.initials: PT
authors.lastname: Choi
authors.forename: Neal H
authors.initials: NH
authors.lastname: Badner
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Brasher
authors.forename: George K
authors.initials: GK
authors.lastname: Dresser
authors.forename: Diego H
authors.initials: DH
authors.lastname: Delgado
authors.forename: W Scott
authors.initials: WS
authors.lastname: Beattie
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D002170:Canada; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control*; D057968:Transdermal Patch; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D003000:Clonidine