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

• ClinicalTrials.gov Identifier: NCT03310125
• Recruitment Status: Completed
• First Posted: October 16, 2017
• Last Update Posted: August 7, 2023
• Sponsor: Population Health Research Institute
• Collaborator: Hamilton Health Sciences Corporation
• Information provided by (Responsible Party): Population Health Research Institute

Tracking Information

• First Submitted Date: October 10, 2017
• First Posted Date: October 16, 2017
• Last Update Posted Date: August 7, 2023
• Actual Study Start Date: February 14, 2018
• Actual Primary Completion Date: July 26, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2022)

• Clinically important perioperative atrial fibrillation/atrial flutter [ Time Frame: 14 days of randomization ]
• Myocardial injury after noncardiac surgery [ Time Frame: 14 days of randomization ]

Original Primary Outcome Measures (submitted: October 10, 2017)

Clinically important atrial fibrillation [ Time Frame: within 14 days of randomization ]

Clinically important AF developing after randomization until the end of follow-up

Current Secondary Outcome Measures (submitted: November 3, 2022)

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

Original Secondary Outcome Measures (submitted: October 10, 2017)

• First occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke [ Time Frame: within 14 days of randomization ]
• Duration of stay in ICU, step-down, and in-hospital [ Time Frame: within 14 days of randomization ]
• All-cause mortality [ Time Frame: within 14 days of randomization ]
• Myocardial infarction [ Time Frame: within 14 days of randomization ]
• Myocardial injury after noncardiac surgery (MINS) [ Time Frame: within 14 days of randomization ]
• Time to chest tube removal [ Time Frame: within 14 days of randomization ]

Current Other Pre-specified Outcome Measures (submitted: November 3, 2022)

• Sepsis or infection [ Time Frame: 14 days of randomization ]
  Safety outcome
• Non-infectious diarrhea [ Time Frame: 14 days of randomization ]
  Safety outcome

Original Other Pre-specified Outcome Measures (submitted: October 10, 2017)

• Sepsis/infection [ Time Frame: within 14 days of randomization ]
  Safety outcome
• Non-infectious diarrhea [ Time Frame: within 14 days of randomization ]
  Safety outcome
• Major bleeding [ Time Frame: within 14 days of randomization ]
  Safety outcome

Descriptive Information

• Brief Title: Colchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery (COP-AF)
• Official Title: Colchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery (COP-AF)
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

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

Intervention

• Drug: Colchicine
  Over-encapsulated 0.5mg tablet twice daily
• Drug: Placebo
  Matching placebo capsule twice daily

Study Arms

• Experimental: Colchicine
  Participants received over-encapsulated colchicine 0.5 mg tablet orally twice daily for 10 days.
  Intervention: Drug: Colchicine
• Placebo Comparator: Placebo
  Participants received matching placebo capsules orally twice daily for 10 days.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 26, 2023): 3209
• Original Estimated Enrollment (submitted: October 10, 2017): 3000
• Actual Study Completion Date: July 26, 2023
• Actual Primary Completion Date: July 26, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, Colombia, Hong Kong, Italy, Malaysia, Pakistan, Spain, Switzerland, United States
• Removed Location Countries: China

Administrative Information

• NCT Number: NCT03310125
• Other Study ID Numbers: 2017-001-COPAF
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Population Health Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Population Health Research Institute
• Original Study Sponsor: Same as current
• 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

• PRS Account: Population Health Research Institute
• Verification Date: August 2023