Colchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery (COP-AF) (COP-AF)

The prevention of perioperative atrial fibrillation (AF) and myocardial injury after non-cardiac surgery (MINS) has the potential to reduce mortality, stroke, and hospital stays in patients undergoing major thoracic surgery. Data from cardiac surgery patients suggest that prevention of perioperative atrial fibrillation using an anti-inflammatory agent, such as colchicine, is feasible. The COP-AF trial will assess whether the administration of oral colchicine will reduce the incidence of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Atrial Flutter; Myocardial Injury After Non-Cardiac Surgery
• Intervention / Treatment: Drug: Colchicine; Drug: Placebo

Detailed Description

Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are among the most common serious complications occurring after thoracic surgery. AF is the most common perioperative cardiac arrhythmia. The incidence of perioperative AF in patients undergoing major thoracic surgery ranges from 10% in low-risk patients to as high as 20% in high-risk patients. The course of patients with perioperative AF is frequently complicated by hemodynamic instability, problems with managing anticoagulation in the early postoperative period, prolonged intensive care unit and hospital stays, and increased costs. Patients who develop perioperative AF (POAF) or MINS also have a significantly increased risk of death and stroke.

Colchicine is an inexpensive drug and a highly effective anti-inflammatory agent that holds great potential for preventing POAF and MINS in patients undergoing thoracic surgery. Data from cardiac surgery patients suggest that prevention of POAF using colchicine is feasible, but whether this concept is also applicable to patients undergoing thoracic surgery, where the risk of POAF is lower and underlying mechanisms may be different, is currently unclear. The 'Colchicine for the prevention of perioperative AF' (COP-AF) trial has been designed as a large randomized, double blind, placebo controlled trial to determine whether colchicine, a potent, safe and inexpensive anti-inflammatory drug, lowers the risk of perioperative AF, MINS, and other inflammatory complications in patients undergoing thoracic surgery. The primary objective of this trial is to determine whether a 10-day course of colchicine 0.5mg twice daily reduces the incidence of perioperative AF and MINS within 14 days after thoracic surgery.

• Study Type: Interventional
• Enrollment (Actual): 3209
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Vienna General Hospital
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme
  • Brussels, Belgium, 1020
    • CHU Brugmann UVC
  • Charleroi, Belgium, 6042
    • Hôpital Civil Marie Curie
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre Winnipeg
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Victoria General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • London, Ontario, Canada, N6A 5W9
      • Victoria Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital General Campus
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Montreal General Hospital
    • Québec, Quebec, Canada, G1V 4G5
      • Institut Universitaire de cardiologie et de pneumologie de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5H3
      • CIUSSS de l'Estrie - CHUS
• Colombia
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia
      • Fundación Cardioinfantil y LaCardio
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
• Italy
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi
  • Milan, Italy, 20132
    • Irccs Ospedale San Raffaele
  • Rome, Italy, 00189
    • Azienda Ospedaliero-Universitaria Sant'Andrea
  • Torino, Italy, 10126
    • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
  • Udine, Italy, 33100
    • Ospedale Santa Maria Della Misericordia
• Malaysia
  • Selangor
    • Kajang, Selangor, Malaysia, 43000
      • Hospital Serdang
    • Kuala Lumpur, Selangor, Malaysia, 59100
      • University of Malaya Medical Centre
• Pakistan
  • Islamabad Capital Territory
    • Islamabad, Islamabad Capital Territory, Pakistan, 44000
      • Shifa International Hospital
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08029
    • Hospital Universitari Sagrat Cor
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañon
• Switzerland
  • Luzern, Switzerland
    • Luzerner Kantonsspital
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich
• United States
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44111
      • Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients are eligible if they:

1. are undergoing thoracic surgery with general anesthesia;
2. are greater than or equal to 55 years of age at the time of randomization;
3. are expected to require at least an overnight hospital admission after surgery; and
4. provide written informed consent to participate.

Exclusion Criteria:

Patients will be excluded if they:

1. have a prior history of documented atrial fibrillation;
2. are currently taking anti-arrhythmic medication other than β-blockers, calcium channels blockers or digoxin;
3. are undergoing minor thoracic interventions/procedures (i.e., minor chest-wall surgeries, chest tube insertions, or needle pleural/lung biopsies);
4. have a contraindication to colchicine (i.e., allergy to colchicine, myelodysplastic disorders, or an estimated glomerular filtration rate less than 30 mL/min/1.73m);
5. are not expected to take oral medications for greater than 24 hours after surgery (e.g., esophagectomy);
6. are scheduled for lung transplantation;
7. are currently taking non-study colchicine before surgery;
8. have severe hepatic dysfunction;
9. have aplastic anemia;
10. are a woman of childbearing potential who is pregnant, breastfeeding, or not taking effective contraception;
11. took within the last 14 days or are scheduled to take during the first 10 days after surgery clarithromycin, erythromycin, telithromycin, cyclosporine, ketoconazole, or itraconazole;
12. are an HIV patient treated with antiretroviral therapy; or
13. are scheduled for thoracoscopic lung wedge resection only.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; Participants received over-encapsulated colchicine 0.5 mg tablet orally twice daily for 10 days.	Drug: Colchicine; Over-encapsulated 0.5mg tablet twice daily
Placebo Comparator: Placebo; Participants received matching placebo capsules orally twice daily for 10 days.	Drug: Placebo; Matching placebo capsule twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinically important perioperative atrial fibrillation/atrial flutter	14 days of randomization
Myocardial injury after noncardiac surgery	14 days of randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
First occurrence of the composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, or nonfatal stroke	14 days of randomization
First occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke	14 days of randomization
First occurrence of myocardial injury after noncardiac surgery not fulfilling the 4th universal definition of myocardial infarction	14 days of randomization
First occurrence of myocardial infarction	14 days of randomization
Time to chest tube removal	14 days of randomization
Duration of stay in ICU, step-down, and in-hospital	14 days of randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sepsis or infection	Safety outcome	14 days of randomization
Non-infectious diarrhea	Safety outcome	14 days of randomization

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: David Conen, MD, MPH, Population Health Research Institute; Study Chair: PJ Devereaux, MD, PhD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2018
• Primary Completion (Actual): July 26, 2023
• Study Completion (Actual): July 26, 2023

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 16, 2017

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Atrial Fibrillation; Randomized; Thoracic Surgery; Colchicine; Myocardial Injury
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 2017-001-COPAF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No