Clinical trial NCT03310125: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Atrial Flutter
Myocardial Injury After Non-Cardiac Surgery
Keywords: Atrial Fibrillation
Inflammation
Thoracic Surgery
Randomized
Colchicine
Myocardial Injury
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
First posted: 2017-10-16
Enrollment: 3209
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Clinically important perioperative atrial fibrillation/atrial flutter
timeFrame: 14 days of randomization
measure: Myocardial injury after noncardiac surgery
timeFrame: 14 days of randomization
Secondary outcomes:
measure: First occurrence of the composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, or nonfatal stroke
timeFrame: 14 days of randomization
measure: First occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke
timeFrame: 14 days of randomization
measure: First occurrence of myocardial injury after noncardiac surgery not fulfilling the 4th universal definition of myocardial infarction
timeFrame: 14 days of randomization
measure: First occurrence of myocardial infarction
timeFrame: 14 days of randomization
measure: Time to chest tube removal
timeFrame: 14 days of randomization
measure: Duration of stay in ICU, step-down, and in-hospital
timeFrame: 14 days of randomization
Other outcomes:
measure: Sepsis or infection
timeFrame: 14 days of randomization
measure: Non-infectious diarrhea
timeFrame: 14 days of randomization
Locations:
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Fairview Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Vienna
country: Austria
facility: Vienna General Hospital
city: Brussels
country: Belgium
facility: CHU Brugmann UVC
city: Brussels
country: Belgium
facility: Hôpital Érasme
city: Charleroi
country: Belgium
facility: Hôpital Civil Marie Curie
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre Winnipeg
state: Manitoba
city: Halifax
country: Canada
facility: Victoria General Hospital
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital General Campus
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - CHUS
state: Quebec
city: Bogotá
country: Colombia
facility: Fundación Cardioinfantil y LaCardio
state: Cundinamarca
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino
city: Udine
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Kajang
country: Malaysia
facility: Hospital Serdang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
state: Selangor
city: Islamabad
country: Pakistan
facility: Shifa International Hospital
state: Islamabad Capital Territory
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Sagrat Cor
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Population Health Research Institute
name: David Conen, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Population Health Research Institute
name: PJ Devereaux, MD, PhD
role: STUDY_CHAIR
References: