COP-AF Pilot: Colchicine For Prevention of Perioperative Atrial Fibrillation in Patients Undergoing Thoracic Surgery Pilot Study

• Sponsor: Population Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01985425
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other)
• Enrollment: 100
• Locations: 2
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 50
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The purpose of this pilot study is to determine the feasibility of comparing colchicine to placebo for the prevention of new onset atrial fibrillation in patients undergoing general thoracic surgery and establish the foundation for a large, multi-centre, clinical trial.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Thoracic Surgery	Drug: Colchicine 0.6 mg; Drug: Placebo Colchicine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Colchicine For Prevention of Perioperative Atrial Fibrillation in Patients Undergoing Thoracic Surgery Pilot Study.
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Colchicine On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days.	Drug: Colchicine 0.6 mg; Other Names: Brand names: PMS Colchicine, Colchicine TAB 0.6 mg
Placebo Comparator: Placebo Colchicine On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days.	Drug: Placebo Colchicine

Outcome Measures

Primary Outcome Measures

1. Clinically Significant Atrial Fibrillation [Post-operative Day 1 until Postoperative Day 30]

   New atrial fibrillation that results in angina, congestive heart failure, symptomatic hypotension, or that requires treatment with a rate controlling drug, antiarrhythmic drug, or electrical cardioversion, or that lasts for longer than 30 seconds.

Secondary Outcome Measures

1. Death [Post-operative Day 1 until Postoperative Day 30]

2. New Onset Atrial Flutter [Post-operative Day 1 until Postoperative Day 30]

   Replacement of the consistent P waves on 12-lead ECG, or documented telemetry tracing, by saw-tooth flutter waves.

3. Myocardial Injury After Non-Cardiac Surgery (MINS) [Post-operative Day 1 until Postoperative Day 30]

   Requires one of the following criteria: A) Elevated troponin or CK-MB measurement with one or more of the following defining features: Ischemic signs or symptoms (i.e., chest, arm, neck, or jaw discomfort; shortness of breath, pulmonary edema); Development of pathologic Q waves present in any two contiguous leads that are >30 milliseconds; Electrocardiogram (ECG) changes indicative of ischemia (i.e., ST segment elevation [>2 mm in leads V1, V2, or V3 OR >1 mm in the other leads], ST segment depression [>1 mm], OR symmetric inversion of T waves >1 mm) in at least two contiguous leads; New LBBB; or v. new or presumed new cardiac wall motion abnormality on echocardiography or new or presumed new fixed defect on radionuclide imaging; B) Elevated troponin measurement after surgery with no alternative explanation (e.g., pulmonary embolism, sepsis) to myocardial injury

4. Stroke [Post-operative Day 1 until Postoperative Day 30]

   New focal neurological deficit thought to be vascular in origin with signs and symptoms lasting more than 24 hours and cerebral imaging consistent with acute stroke.

5. Transient Ischemic Attack (TIA) [Post-operative Day 1 until Postoperative Day 30]

   New focal neurological deficit thought to be vascular in origin with signs and symptoms lasting less than 24 hours.

6. Post-operative Infection [Post-operative Day 1 until Postoperative Day 30]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• All patients ≥55 years of age undergoing intra-thoracic surgery for a resection of tumor in lung.

Exclusion Criteria:

• In AF prior to surgery*,

• Undergoing minor thoracic interventions/ procedures (i.e., chest tube insertion, needle pleural/lung biopsies, or minor chest-wall surgeries), or

• With contraindications to colchicine (i.e., allergy, or myelodysplastic disorders or estimated glomerular filtration rate [e-GFR] <30 mL/min/1.73m)

• Clarification: Patients with history of AF who are in sinus rhythm during enrollment will be eligible for recruitment. Patients who have no history of AF and are found to be in AF at the time of enrollment will not be eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Manitoba Health Sciences Centre	Winnipeg	Manitoba	Canada	R3A 1R9
2	St. Joseph Healthcare, St. Joseph Hospital	Hamilton	Ontario	Canada	L8N 4A6

Sponsors and Collaborators

• Population Health Research Institute
• Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: PJ Devereaux, PhD, McMaster University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT01985425
• Other Study ID Numbers: COP-AF Pilot
• First Posted: Nov 15, 2013
• Last Update Posted: Nov 5, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Atrial Fibrillation; Colchicine

Study Results

Participant Flow

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Period Title: Overall Study
STARTED	49	51
COMPLETED	49	51
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active Colchicine	Placebo Colchicine	Total
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo	Total of all reporting groups
Overall Participants	49	51	100
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 34.7%	18 35.3%	35 35%
>=65 years	32 65.3%	33 64.7%	65 65%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.89 (7.5)	68.28 (7.4)	68.57 (7.4)
Sex: Female, Male (Count of Participants)
Female	33 67.3%	22 43.1%	55 55%
Male	16 32.7%	29 56.9%	45 45%
Region of Enrollment (participants) [Number]
Canada	49 100%	51 100%	100 100%

Outcome Measures

1. Primary Outcome

Title	Clinically Significant Atrial Fibrillation
Description	New atrial fibrillation that results in angina, congestive heart failure, symptomatic hypotension, or that requires treatment with a rate controlling drug, antiarrhythmic drug, or electrical cardioversion, or that lasts for longer than 30 seconds.
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	5 10.2%	6 11.8%

2. Secondary Outcome

Title	Death
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	New Onset Atrial Flutter
Description	Replacement of the consistent P waves on 12-lead ECG, or documented telemetry tracing, by saw-tooth flutter waves.
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	0 0%	1 2%

4. Secondary Outcome

Title	Myocardial Injury After Non-Cardiac Surgery (MINS)
Description	Requires one of the following criteria: A) Elevated troponin or CK-MB measurement with one or more of the following defining features: Ischemic signs or symptoms (i.e., chest, arm, neck, or jaw discomfort; shortness of breath, pulmonary edema); Development of pathologic Q waves present in any two contiguous leads that are >30 milliseconds; Electrocardiogram (ECG) changes indicative of ischemia (i.e., ST segment elevation [>2 mm in leads V1, V2, or V3 OR >1 mm in the other leads], ST segment depression [>1 mm], OR symmetric inversion of T waves >1 mm) in at least two contiguous leads; New LBBB; or v. new or presumed new cardiac wall motion abnormality on echocardiography or new or presumed new fixed defect on radionuclide imaging; B) Elevated troponin measurement after surgery with no alternative explanation (e.g., pulmonary embolism, sepsis) to myocardial injury
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	10 20.4%	12 23.5%

5. Secondary Outcome

Title	Stroke
Description	New focal neurological deficit thought to be vascular in origin with signs and symptoms lasting more than 24 hours and cerebral imaging consistent with acute stroke.
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Transient Ischemic Attack (TIA)
Description	New focal neurological deficit thought to be vascular in origin with signs and symptoms lasting less than 24 hours.
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Post-operative Infection
Time Frame	Post-operative Day 1 until Postoperative Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Colchicine	Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine	On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
Measure Participants	49	51
Count of Participants [Participants]	6 12.2%	8 15.7%

Adverse Events

Arm/Group Title	Active Colchicine		Placebo Colchicine
Arm/Group Description	On the day of surgery, the intervention group will receive 2 doses of colchicine 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine		On the day of surgery, the intervention group will receive 2 doses of colchicine placebo 0.6 mg orally. The first dose will be administered within 4 hours before surgery. The second dose will be given between 6:00PM and 11:59PM after surgery. All patients will receive colchicine 0.6 mg or placebo twice daily orally for 10 days. Colchicine Placebo
All Cause Mortality
	Active Colchicine		Placebo Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active Colchicine		Placebo Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/49 (6.1%)		3/51 (5.9%)
Cardiac disorders
unconsciousness	0/49 (0%)	0	1/51 (2%)	1
Nervous system disorders
fall	2/49 (4.1%)	2	0/51 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	3/49 (6.1%)	3	2/51 (3.9%)	2
Other (Not Including Serious) Adverse Events
	Active Colchicine		Placebo Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.