Atrial FibrillationPhase 3COP-AFNCT03310125
Colchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery (COP-AF)
A Phase 3 study testing Active Colchicine in people with Atrial Fibrillation and Atrial Flutter, run by Population Health Research Institute at 46 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Atrial Fibrillation, Atrial Flutter, Myocardial Injury After Non-Cardiac Surgery
- What is being tested?
- Active Colchicine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,209 participants
- Where
- 46 sitesin 11 countries
- Study dates
- 14 Feb 2018to 23 Jun 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients are eligible if they:
- are undergoing thoracic surgery with general anesthesia;
- are greater than or equal to 55 years of age at the time of randomization;
- are expected to require at least an overnight hospital admission after surgery; and
- provide written informed consent to participate.
Who cannot join
- We will exclude patients who meet any of the following criteria:
- patients with a prior history of documented AF;
- patients currently taking anti-arrhythmic medication other than β-blockers, calcium channels blockers or digoxin;
- patients undergoing minor thoracic interventions/procedures (i.e., minor chest-wall surgeries, chest tube insertions, or needle pleural/lung biopsies);
- patients with contraindications to colchicine (i.e., allergy to colchicine, myelodysplastic disorders, or an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m);
- patients not expected to take oral medications for >24 hours after surgery (e.g., esophagectomy);
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- patients scheduled for lung transplantation;
- patients currently taking non-study colchicine before surgery;
- patients with severe hepatic dysfunction;
- patients with aplastic anemia;
- women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding;
- patients who took within the last 14 days or scheduled to take during the first 10 days after surgery clarithromycin, erythromycin, telithromycin, cyclosporine, ketoconazole, or itraconazole* (While systemic administration of these medications is contraindicated, patients with local administration only (e.g., eye drops, creams) are eligible for the trial);
- human immunodeficiency virus (HIV) patients treated with antiretroviral therapy; or
- patients scheduled for thoracoscopic lung wedge resection only†. (Patients scheduled for multiple thoracoscopic lung wedge resection only are eligible for inclusion).
Trial locations and contacts
46 sites in 11 countries.
46 sites in 11 countries
Canada13 sites
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
Victoria General Hospital
Halifax, Nova Scotia, B3H 2Y9
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Kingston General Hospital
Kingston, Ontario, K7L 2V7
Victoria Hospital
London, Ontario, N6A 5W9
Montreal General Hospital
Montreal, Quebec, H3G 1A4
The Ottawa Hospital General Campus
Ottawa, Ontario, K1H 8L6
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec, G1V 4G5
CIUSSS de l'Estrie - CHUS
Sherbrooke, Quebec, J1H 5H3
Toronto General Hospital
Toronto, Ontario, M5G 2C4
St. Joseph's Health Centre
Toronto, Ontario
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Health Sciences Centre Winnipeg
Winnipeg, Manitoba, R3A 1R9
United States8 sites
Fairview Hospital
Cleveland, Ohio, 44111
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Henry Ford Hospital
Detroit, Michigan, 48202
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Rhode Island Hospital
Providence, Rhode Island, 02903
Stony Brook University Hospital
Stony Brook, New York, 11794
Cleveland Clinic Florida
Weston, Florida, 33331
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
Spain7 sites
Hospital del Mar
Barcelona, 08003
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitari Sagrat Cor
Barcelona, 08029
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Clínic de Barcelona
Barcelona, 08036
Hospital Gregorio Maranon
Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, 28034
Italy6 sites
Azienda Ospedaliero Universitaria Careggi
Florence, Florence, 50134
IRCCS Ospedale San Raffaele
Milan, 20132
Fondazione Policlinico Universitario A. Gemelli IRCCS
Roma
Azienda Ospedaliero-Universitaria Sant'Andrea
Rome, 00189
Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
Torino, 10126
Ospedale Santa Maria della Misericordia
Udine, Udine, 33100
Belgium3 sites
CHU Brugmann UVC
Brussels, Brussels Capital, 1020
Hôpital Érasme
Brussels, 1070
Hôpital Civil Marie Curie
Charleroi, 6042
Hong Kong2 sites
Prince of Wales Hospital
Hong Kong, Hong Kong
Tuen Mun Hospital
Hong Kong
Malaysia2 sites
Hospital Serdang
Kajang, Selangor, 43000
University of Malaya Medical Centre
Kuala Lumpur, Selangor, 59100
Switzerland2 sites
Luzerner Kantonsspital
Lucerne
Universitätsspital Zürich
Zurich, 8091
About this study
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.
- Being tested
- Active Colchicine, Active Placebo
- Keywords
- Atrial Fibrillation, Inflammation, Thoracic Surgery, Randomized, Colchicine, Myocardial Injury
- Medical subject headings
- Atrial Fibrillation, Atrial Flutter, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active ColchicineDrug
Oral colchicine 0·5 mg twice daily, starting within 4 h before surgery and continuing for 10 days.
Active PlaceboDrug
Oral placebo 0·5 mg twice daily, starting within 4 h before surgery and continuing for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Active Colchicine | Experimental | Oral colchicine 0·5 mg twice daily, starting within 4 h before surgery and continuing for 10 days Receives: Drug: Active Colchicine |
| Active Placebo | Placebo comparator | Oral placebo 0·5 mg twice daily, starting within 4 h before surgery and continuing for 10 days. Receives: Drug: Active Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically Important Perioperative Atrial Fibrillation
Clinically important perioperative atrial fibrillation was defined as atrial fibrillation or atrial flutter that results in angina, heart failure, or symptomatic hypotension, or that requires treatment with a rate-controlling drug, anti-arrhythmic drug, or electrical cardioversion.
Measured: 14 days after randomisation
Number of Participants With Myocardial Injury After Non-cardiac Surgery (MINS)
Measured: 14 days after randomisation
Secondary outcomes (8)
Number of Participants With Composite of All-cause Death, Non-fatal MINS, and Non-fatal Stroke
Measured: 14 days after randomisation
Number of Participants With Composite of All-cause Death, Non-fatal Myocardial Infarction, and Non-fatal Stroke
Measured: 14 days after randomisation
Number of Participants With MINS Not Fulfilling the Fourth Universal Definition of Myocardial Infarction
Measured: 14 days after randomisation
Number of Participants With Myocardial Infarction
Measured: 14 days after randomisation
Time to Chest Tube Removal, Days
Measured: 14 days after randomisation
Days in Hospital
Measured: 14 days after randomisation
Nights in Step-down Unit
Measured: 14 days after randomisation
Nights in Intensive Care Unit
Measured: 14 days after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2017
- Study start14 Feb 2018
- Primary completion1 Jun 2023
- Study completion23 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,209 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation
- Responsible party
- Sponsor
- Investigators
- David Conen, MD, MPH, Principal investigator, Population Health Research InstitutePJ Devereaux, MD, PhD, Study chair, Population Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03310125
- Sponsor's protocol ID
- 2017-001-COPAF
- Acronym
- COP-AF
- Status last verified
- Jun 2025
- First submitted
- 10 Oct 2017
- Last updated
- 16 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Conen D, Popova E, Wang MK, Chan MTV, Landoni G, Reimer C, Srinathan SK, Cata JP, McLean SR, Trujillo Reyes JC, Grande AM, Gonzalez Tallada A, Sessler DI, Fleischmann E, Maziak DE, Kabon B, Voltolini L, Gutierrez-Soriano L, Tandon V, DuMerton D, Kidane B, Rajaram R, Shargall Y, Neary JD, Wells JR, McIntyre WF, Blum S, Ofori SN, Vincent J, Xu L, Li Z, Healey JS, Garg AX, Devereaux PJ; COP-AF Investigators. Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial. Am Heart J. 2023 May;259:87-96. doi: 10.1016/j.ahj.2023.01.018. Epub 2023 Feb 7.
PubMed 36754105Conen D, Ke Wang M, Popova E, Chan MTV, Landoni G, Cata JP, Reimer C, McLean SR, Srinathan SK, Reyes JCT, Grande AM, Tallada AG, Sessler DI, Fleischmann E, Kabon B, Voltolini L, Cruz P, Maziak DE, Gutierrez-Soriano L, McIntyre WF, Tandon V, Martinez-Tellez E, Guerra-Londono JJ, DuMerton D, Wong RHL, McGuire AL, Kidane B, Roux DP, Shargall Y, Wells JR, Ofori SN, Vincent J, Xu L, Li Z, Eikelboom JW, Jolly SS, Healey JS, Devereaux PJ; COP-AF Investigators. Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial. Lancet. 2023 Nov 4;402(10413):1627-1635. doi: 10.1016/S0140-6736(23)01689-6. Epub 2023 Aug 25.
PubMed 37640035Ofori S, Wang MK, Popova E, McIntyre WF, Chan M, Sessler DI, Giulia V, Warwas M, Balasubramanian K, Tandon V, Finley C, Anna GT, Cata J, Srinathan S, Reimer C, McLean S, Trujillo JC, Fleischmann E, Voltolini L, Cruz P, Maziak DE, Gutierrez-Soriano L, Amir M, Bossard M, Wang CY, Devereaux PJ, Conen D; COP-AF investigators. Smoking, Colchicine and Postoperative Outcomes in Thoracic Surgery: Post Hoc Analysis of the COP-AF Randomized Controlled Trial. CJC Open. 2025 Apr 21;7(7):860-870. doi: 10.1016/j.cjco.2025.04.008. eCollection 2025 Jul.
PubMed 40698308Garg AX, Cuerden M, Cata J, Chan MTV, Devereaux PJ, Fleischmann E, Grande AM, Kabon B, Landoni G, Maziak DE, McLean S, Parikh C, Popova E, Reimer C, Trujillo Reyes JC, Roshanov P, Sessler DI, Srinathan S, Sontrop JM, Gonzalez Tallada A, Wang MK, Wells JR, Conen D. Effect of Colchicine on the Risk of Perioperative Acute Kidney Injury: Clinical Protocol of a Substudy of the Colchicine for the Prevention of Perioperative Atrial Fibrillation Randomized Clinical Trial. Can J Kidney Health Dis. 2023 Jul 11;10:20543581231185427. doi: 10.1177/20543581231185427. eCollection 2023.
PubMed 37457622