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

NCT ID: NCT03310125

Last Updated: 2023-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3209 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-14
• Study Completion Date: 2023-07-26

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Colchicine

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

Group Type: EXPERIMENTAL

Colchicine

Intervention Type: DRUG

Over-encapsulated 0.5mg tablet twice daily

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo capsule twice daily

Interventions

Colchicine

Over-encapsulated 0.5mg tablet twice daily

Intervention Type: DRUG

Placebo

Matching placebo capsule twice daily

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

Population Health Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Conen, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

PJ Devereaux, MD, PhD

Role: STUDY_CHAIR

Population Health Research Institute

Locations

Cleveland Clinic Florida

Weston, Florida, United States

Henry Ford Hospital

Detroit, Michigan, United States

Stony Brook University Hospital

Stony Brook, New York, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Fairview Hospital

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Rhode Island Hospital

Providence, Rhode Island, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Vienna General Hospital

Vienna, , Austria

CHU Brugmann UVC

Brussels, , Belgium

Hôpital Érasme

Brussels, , Belgium

Hôpital Civil Marie Curie

Charleroi, , Belgium

Foothills Medical Centre

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Health Sciences Centre Winnipeg

Winnipeg, Manitoba, Canada

Victoria General Hospital

Halifax, Nova Scotia, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

Victoria Hospital

London, Ontario, Canada

The Ottawa Hospital General Campus

Ottawa, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Montreal General Hospital

Montreal, Quebec, Canada

Institut universitaire de cardiologie et de pneumologie de Québec

Québec, Quebec, Canada

CIUSSS de l'Estrie - CHUS

Sherbrooke, Quebec, 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, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, , Italy

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Torino, , Italy

Ospedale Santa Maria della Misericordia

Udine, , Italy

Hospital Serdang

Kajang, Selangor, Malaysia

University of Malaya Medical Centre

Kuala Lumpur, Selangor, Malaysia

Shifa International Hospital

Islamabad, Islamabad, Pakistan

Hospital del Mar

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitari Sagrat Cor

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Gregorio Maranon

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Luzerner Kantonsspital

Lucerne, , Switzerland

Universitätsspital Zürich

Zurich, , Switzerland

Countries

United States; Austria; Belgium; Canada; Colombia; Hong Kong; Italy; Malaysia; Pakistan; Spain; Switzerland

References

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.

Reference Type: DERIVED

PMID: 40698308 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37640035 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37457622 (View on PubMed)

Other Identifiers

2017-001-COPAF

Identifier Type: -

Identifier Source: org_study_id