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

NCT03310125 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 2017-001-COPAF
• Study Type: interventional
• Target: 3,209
• Locations: 11 countries
• Sites: 44

Brief 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.

Conditions

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

Keywords

Atrial Fibrillation; Inflammation; Thoracic Surgery; Randomized; Colchicine; Myocardial Injury

Outcome Measures

Primary Outcomes (2)

• Clinically important perioperative atrial fibrillation/atrial flutter

  14 days of randomization

• Myocardial injury after noncardiac surgery

  14 days of randomization

Secondary Outcomes (6)

• 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

Other Outcomes (2)

• Sepsis or infection

  14 days of randomization

• Non-infectious diarrhea

  14 days of randomization

Study Arms (2)

Colchicine

EXPERIMENTAL

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

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Colchicine DRUG

Over-encapsulated 0.5mg tablet twice daily

Colchicine

Placebo DRUG

Matching placebo capsule twice daily

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients will be excluded if they:
• have a prior history of documented atrial fibrillation;
• are currently taking anti-arrhythmic medication other than β-blockers, calcium channels blockers or digoxin;
• are undergoing minor thoracic interventions/procedures (i.e., minor chest-wall surgeries, chest tube insertions, or needle pleural/lung biopsies);
• 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);
• are not expected to take oral medications for greater than 24 hours after surgery (e.g., esophagectomy);
• are scheduled for lung transplantation;
• are currently taking non-study colchicine before surgery;
• have severe hepatic dysfunction;
• have aplastic anemia;
• are a woman of childbearing potential who is pregnant, breastfeeding, or not taking effective contraception;
• 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;
• are an HIV patient treated with antiretroviral therapy; or
• are scheduled for thoracoscopic lung wedge resection only.

Sponsors & Collaborators

• Population Health Research Institute: lead
• Hamilton Health Sciences Corporation: collaborator

Study Sites (44)

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Vienna General Hospital

Vienna, 1090, Austria

Location

CHU Brugmann UVC

Brussels, 1020, Belgium

Location

Hôpital Érasme

Brussels, 1070, Belgium

Location

Hôpital Civil Marie Curie

Charleroi, 6042, Belgium

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Health Sciences Centre Winnipeg

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Victoria General Hospital

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

The Ottawa Hospital General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Institut universitaire de cardiologie et de pneumologie de Québec

Québec, Quebec, G1V 4G5, Canada

Location

CIUSSS de l'Estrie - CHUS

Sherbrooke, Quebec, J1H 5H3, Canada

Location

Fundación Cardioinfantil y LaCardio

Bogotá, Cundinamarca, Colombia

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, 00189, Italy

Location

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Ospedale Santa Maria della Misericordia

Udine, 33100, Italy

Location

Hospital Serdang

Kajang, Selangor, 43000, Malaysia

Location

University of Malaya Medical Centre

Kuala Lumpur, Selangor, 59100, Malaysia

Location

Shifa International Hospital

Islamabad, Islamabad, 44000, Pakistan

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Sagrat Cor

Barcelona, 08029, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Luzerner Kantonsspital

Lucerne, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (3)

• Ofori 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.

  PMID: 40698308 DERIVED

• Conen 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.

  PMID: 37640035 DERIVED

• Garg 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.

  PMID: 37457622 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter; Inflammation

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• David Conen, MD, MPH

  Population Health Research Institute

  PRINCIPAL INVESTIGATOR

• PJ Devereaux, MD, PhD

  Population Health Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 16, 2017
• Study Start: February 14, 2018
• Primary Completion: July 26, 2023
• Study Completion: July 26, 2023
• Last Updated: August 7, 2023

Record last verified: 2023-08

Locations

CA (12); CH (2); HK (2); PA (1); BE (3); CO (1); AU (1); ES (7); IT (5); US (8); MY (2)