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

Sponsor

Population Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03310125

Collaborator

Hamilton Health Sciences Corporation (Other)

2,800

Enrollment

Locations

Arms

61.5

Anticipated Duration (Months)

60.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The prevention of perioperative atrial fibrillation has the potential to reduce mortality, stroke, and hospital stays in patients undergoing 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 in patients undergoing major thoracic surgery.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Atrial Flutter	Drug: Colchicine Drug: Placebo	Phase 3

Detailed Description

Atrial fibrillation (AF) is one of the most common serious complications occurring after thoracic surgery and 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) 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 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 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 within 14 days after thoracic surgery.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 14, 2018

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Colchicine Participants received over-encapsulated colchicine 0.5 mg tablet orally twice daily for 10 days.	Drug: Colchicine Over-encapsulated 0.5mg tablet twice daily
Placebo Comparator: Placebo Participants received matching placebo capsules orally twice daily for 10 days.	Drug: Placebo Matching placebo capsule twice daily

Arm

Intervention/Treatment

Experimental: Colchicine

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

Drug: Colchicine

Over-encapsulated 0.5mg tablet twice daily

Placebo Comparator: Placebo

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

Drug: Placebo

Matching placebo capsule twice daily

Outcome Measures

Primary Outcome Measures

Clinically important perioperative atrial fibrillation/atrial flutter [14 days of randomization]

Secondary Outcome Measures

First occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke [14 days of randomization]
Occurrence of myocardial injury after noncardiac surgery [14 days of randomization]
Number of days alive and at home [14 days of randomization]
Time to chest tube removal [14 days of randomization]
Duration of stay in ICU, step-down, and in-hospital [14 days of randomization]
All-cause mortality [14 days of randomization]
Occurrence of myocardial infarction [14 days of randomization]

Other Outcome Measures

Sepsis/infection [14 days of randomization]
Safety outcome
Non-infectious diarrhea [14 days of randomization]
Safety outcome
Life-threatening or major bleeding [14 days of randomization]
Safety outcome

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Florida	Weston	Florida	United States	33331
2	Henry Ford Hospital	Detroit	Michigan	United States	48202
3	Stony Brook University Hospital	Stony Brook	New York	United States	11794
4	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
5	Fairview Hospital	Cleveland	Ohio	United States	44111
6	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
7	Rhode Island Hospital	Providence	Rhode Island	United States	02903
8	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
9	Vienna General Hospital	Vienna		Austria	1090
10	CHU Brugmann UVC	Brussels		Belgium	1020
11	Hôpital Érasme	Brussels		Belgium	1070
12	Hôpital Civil Marie Curie	Charleroi		Belgium	6042
13	Foothills Medical Centre	Calgary	Alberta	Canada	T2N 2T9
14	Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
15	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
16	Health Sciences Centre Winnipeg	Winnipeg	Manitoba	Canada	R3A 1R9
17	Victoria General Hospital	Halifax	Nova Scotia	Canada	B3H 2Y9
18	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N 4A6
19	Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
20	Victoria Hospital	London	Ontario	Canada	N6A 5W9
21	The Ottawa Hospital General Campus	Ottawa	Ontario	Canada	K1H 8L6
22	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
23	Montreal General Hospital	Montreal	Quebec	Canada	H3G 1A4
24	Institut universitaire de cardiologie et de pneumologie de Québec	Québec	Quebec	Canada	G1V 4G5
25	CIUSSS de l'Estrie - CHUS	Sherbrooke	Quebec	Canada	J1H 5H3
26	Fundación Cardioinfantil y LaCardio	Bogotá	Cundinamarca	Colombia
27	Prince of Wales Hospital	Hong Kong		Hong Kong
28	Tuen Mun Hospital	Hong Kong		Hong Kong
29	Azienda Ospedaliero Universitaria Careggi	Florence		Italy	50134
30	IRRCS Ospedale San Raffaele	Milan		Italy	20132
31	Azienda Ospedaliero-Universitaria Sant'Andrea	Rome		Italy	00189
32	Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino	Torino		Italy	10126
33	Ospedale Santa Maria della Misericordia	Udine		Italy	33100
34	Hospital Serdang	Kajang	Selangor	Malaysia	43000
35	University of Malaya Medical Centre	Kuala Lumpur	Selangor	Malaysia	59100
36	Shifa International Hospital	Islamabad	Islamabad Capital Territory	Pakistan	44000
37	Rehman Medical Institute	Peshawar	Khyber Pakhtunkhwa	Pakistan	25000
38	Hospital del Mar	Barcelona		Spain	08003
39	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
40	Hospital Universitari Sagrat Cor	Barcelona		Spain	08029
41	Hospital Vall d'Hebron	Barcelona		Spain	08035
42	Hospital Clínic de Barcelona	Barcelona		Spain	08036
43	Hospital Gregorio Maranon	Madrid		Spain	28007
44	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
45	Luzerner Kantonsspital	Luzern		Switzerland
46	Universitätsspital Zürich	Zürich		Switzerland	8091

Sponsors and Collaborators

Population Health Research Institute
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