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CompletedNCT03310125COP-AFUpdated Aug 7, 2023

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

A Phase 3 interventional study of Colchicine and Placebo in Atrial Fibrillation, Atrial Flutter and Myocardial Injury After Non-Cardiac Surgery, sponsored by Population Health Research Institute. Completed at 44 sites in 11 countries. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2023-08-07.

Sponsored by Population Health Research Institute · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
3,209
Allocation
Randomized
Ages
55 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Atrial Fibrillation
  • Atrial Flutter
  • Myocardial Injury After Non-Cardiac Surgery

Keywords

  • Atrial Fibrillation
  • Inflammation
  • Thoracic Surgery
  • Randomized
  • Colchicine
  • Myocardial Injury
03

Who can participate

Ages eligible
55 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
3,209 participants (actual)

Study arms

  • Experimental
    Colchicine

    Participants received over-encapsulated colchicine 0.5 mg tablet orally twice daily for 10 days.

    Drug: Colchicine

  • Placebo comparator
    Placebo

    Participants received matching placebo capsules orally twice daily for 10 days.

    Drug: Placebo

Interventions

  • DrugColchicine

    Over-encapsulated 0.5mg tablet twice daily

  • DrugPlacebo

    Matching placebo capsule twice daily

05

What researchers measure

Primary outcomes

  1. Clinically important perioperative atrial fibrillation/atrial flutter

    Time frame: 14 days of randomization

  2. Myocardial injury after noncardiac surgery

    Time frame: 14 days of randomization

Secondary outcomes

  1. First occurrence of the composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, or nonfatal stroke

    Time frame: 14 days of randomization

  2. First occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke

    Time frame: 14 days of randomization

  3. First occurrence of myocardial injury after noncardiac surgery not fulfilling the 4th universal definition of myocardial infarction

    Time frame: 14 days of randomization

  4. First occurrence of myocardial infarction

    Time frame: 14 days of randomization

  5. Time to chest tube removal

    Time frame: 14 days of randomization

  6. Duration of stay in ICU, step-down, and in-hospital

    Time frame: 14 days of randomization

Other outcomes

  1. Sepsis or infection

    Safety outcome

    Time frame: 14 days of randomization

  2. Non-infectious diarrhea

    Safety outcome

    Time frame: 14 days of randomization

06

Study locations

44 sites
  • Cleveland Clinic Florida
    Weston, Florida 33331, United States
  • Henry Ford Hospital
    Detroit, Michigan 48202, United States
  • Stony Brook University Hospital
    Stony Brook, New York 11794, United States
  • Wake Forest Baptist Medical Center
    Winston-Salem, North Carolina 27157, United States
  • Fairview Hospital
    Cleveland, Ohio 44111, United States
  • The Ohio State University Wexner Medical Center
    Columbus, Ohio 43210, United States
  • Rhode Island Hospital
    Providence, Rhode Island 02903, United States
  • The University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Vienna General Hospital
    Vienna, 1090, Austria
  • CHU Brugmann UVC
    Brussels, 1020, Belgium
  • Hôpital Érasme
    Brussels, 1070, Belgium
  • Hôpital Civil Marie Curie
    Charleroi, 6042, Belgium
  • Foothills Medical Centre
    Calgary, Alberta T2N 2T9, Canada
  • Vancouver General Hospital
    Vancouver, British Columbia V5Z 1M9, Canada
  • Health Sciences Centre Winnipeg
    Winnipeg, Manitoba R3A 1R9, Canada
  • Victoria General Hospital
    Halifax, Nova Scotia B3H 2Y9, Canada
  • St. Joseph's Healthcare Hamilton
    Hamilton, Ontario L8N 4A6, Canada
  • Kingston General Hospital
    Kingston, Ontario K7L 2V7, Canada
  • Victoria Hospital
    London, Ontario N6A 5W9, Canada
  • The Ottawa Hospital General Campus
    Ottawa, Ontario K1H 8L6, Canada
  • Toronto General Hospital
    Toronto, Ontario M5G 2C4, Canada
  • Montreal General Hospital
    Montreal, Quebec H3G 1A4, Canada
  • Institut universitaire de cardiologie et de pneumologie de Québec
    Québec, Quebec G1V 4G5, Canada
  • CIUSSS de l'Estrie - CHUS
    Sherbrooke, Quebec J1H 5H3, Canada
  • Fundación Cardioinfantil y LaCardio
    Bogotá, Cundinamarca, Colombia
  • Prince of Wales Hospital
    Hong Kong, Hong Kong
  • Tuen Mun Hospital
    Hong Kong, Hong Kong
  • Azienda Ospedaliero Universitaria Careggi
    Florence, 50134, Italy
  • IRCCS Ospedale San Raffaele
    Milan, 20132, Italy
  • Azienda Ospedaliero-Universitaria Sant'Andrea
    Rome, 00189, Italy
  • Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
    Torino, 10126, Italy
  • Ospedale Santa Maria della Misericordia
    Udine, 33100, Italy
  • Hospital Serdang
    Kajang, Selangor 43000, Malaysia
  • University of Malaya Medical Centre
    Kuala Lumpur, Selangor 59100, Malaysia
  • Shifa International Hospital
    Islamabad, Islamabad Capital Territory 44000, Pakistan
  • Hospital del Mar
    Barcelona, 08003, Spain
  • Hospital de la Santa Creu i Sant Pau
    Barcelona, 08025, Spain
  • Hospital Universitari Sagrat Cor
    Barcelona, 08029, Spain
  • Hospital Vall d'Hebron
    Barcelona, 08035, Spain
  • Hospital Clínic de Barcelona
    Barcelona, 08036, Spain
  • Hospital Gregorio Maranon
    Madrid, 28007, Spain
  • Hospital Universitario Ramón y Cajal
    Madrid, 28034, Spain
  • Luzerner Kantonsspital
    Luzern, Switzerland
  • Universitätsspital Zürich
    Zürich, 8091, Switzerland
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03310125
Lead sponsor
Population Health Research Institute
Collaborators
Hamilton Health Sciences Corporation
Responsible party
Sponsor
First posted
Oct 16, 2017
Start date
Feb 14, 2018
Primary completion
Jul 26, 2023
Completion
Jul 26, 2023
Last update
Aug 7, 2023

Study contacts

David Conen, MD, MPH
principal investigator · Population Health Research Institute
PJ Devereaux, MD, PhD
study chair · Population Health Research Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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