END-AF: Effect of Colchicine on the Incidence of Atrial Fibrillation in Open Heart Surgery Patients

• Sponsor: Jordan Collaborating Cardiology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT03021343
• Collaborator: (none)
• Enrollment: 360
• Arms: 2
• Duration (Months): 28

Study Details

Study Description

Brief Summary

This study evaluates the role of colchicine in the prevention of atrial fibrillation in patients undergoing open heart surgery. Half of participants will receive colchicine and the other half will not

Condition or Disease	Intervention/Treatment	Phase
Arrhythmia	Drug: Colchicine	Phase 3

Detailed Description

Atrial fibrillation (AF) is the most common arrhythmia in patients undergoing cardiac surgery and is estimated to occur in 26% of all cardiac surgery patients. It can lead to increase morbidity, mainly due to hemodynamic instability and thromboembolic complications, and to increased hospital stay with its associated higher health care cost.

Previous studies have demonstrated that increased inflammation may precede AF and, therefore, interventions that reduce the inflammatory process may help reduce the incidence of AF. Colchicine has potent anti-inflammatory properties and may therefore be capable of reducing the incidence of AF.

This study aims to determine whether the administration of colchicine starting the day before cardiac surgery and continuing until discharge may lead to reduction in post-operative AF.

Study Design

• Study Type: Interventional
• Actual Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Effect of ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart Surgery Patients: END-AF Trial
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Colchicine Colchicine 2 mg 12-24 hours prior to surgery and 1 mg 4 hours before or immediately after surgery and then continued at a dose of 0.5 mg twice daily until hospital discharge. Half the dose was given to patients weighing <70 kg or intolerant to the full dose.	Drug: Colchicine; colchicine given as per trial protocol
No Intervention: No colchicine In this arm no active medication was administered

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Atrial Fibrillation [From date of randomization until the date of discharge, assessed up to 2 weeks]

   The primary efficacy end point was the rate of AF in both arms. AF lasting more than 5 minutes were considered significant

2. The Number of Participants With Colchicine Side Effects [From date of randomization until the date of discharge, assessed up to 2 weeks]

   The primary safety endpoint was the occurrence of side effects. Side effects monitored were mainly gastrointestinal effects (especially diarrhoea), alopecia, anorexia, hepatotoxicity, myotoxicity, and bone marrow toxicity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All consecutive adult patients undergoing elective cardiac surgery

Exclusion Criteria:

• Documented history of AF or supraventricular arrhythmia or, absence of sinus rhythm on hospital admission

• Known severe liver disease or current transaminases >1.5 times the upper normal limit

• Current serum creatinine >2.5 mg/dl

• Known myopathy or elevated baseline preoperative creatine kinase

• Known blood dyscrasias

• Significant gastrointestinal disease

• Pregnant and lactating women

• Known hypersensitivity to colchicine

• Current treatment with colchicine for any indications

• Emergency surgery

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Jordan Collaborating Cardiology Group

Investigators

• Principal Investigator: Ramzi A Tabbalat, MD, FACC, Khalidi Hospital and Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jordan Collaborating Cardiology Group
• ClinicalTrials.gov Identifier: NCT03021343
• Other Study ID Numbers: KMC-JCC
• First Posted: Jan 13, 2017
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Jordan Collaborating Cardiology Group: Atrial fibrillation; Colchicine; Cardiac surgery
• Additional relevant MeSH terms: Atrial Fibrillation; Colchicine

Study Results

Participant Flow

Arm/Group Title	Colchicine	No Colchicine
Arm/Group Description	Colchicine 2 mg 12-24 hours prior to surgery and 1 mg 4 hours before or immediately after surgery and then continued at a dose of 0.5 mg twice daily until hospital discharge. Half the dose was given to patients weighing <70 kg or intolerant to the full dose. Colchicine: colchicine given as per trial protocol	In this arm no active medication was administered
Period Title: Overall Study
STARTED	179	181
COMPLETED	174	174
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Colchicine	No Colchicine	Total
Arm/Group Description	Colchicine 2 mg 12-24 hours prior to surgery and 1 mg 4 hours before or immediately after surgery and then continued at a dose of 0.5 mg twice daily until hospital discharge. Half the dose was given to patients weighing <70 kg or intolerant to the full dose. Colchicine: colchicine given as per trial protocol	In this arm no active medication was administered	Total of all reporting groups
Overall Participants	179	181	360
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60.8	60.5	60.6
Sex: Female, Male (Count of Participants)
Female	38 21.2%	38 21%	76 21.1%
Male	141 78.8%	143 79%	284 78.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Atrial Fibrillation
Description	The primary efficacy end point was the rate of AF in both arms. AF lasting more than 5 minutes were considered significant
Time Frame	From date of randomization until the date of discharge, assessed up to 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	No Colchicine
Arm/Group Description	Colchicine 2 mg 12-24 hours prior to surgery and 1 mg 4 hours before or immediately after surgery and then continued at a dose of 0.5 mg twice daily until hospital discharge. Half the dose was given to patients weighing <70 kg or intolerant to the full dose. Colchicine: colchicine given as per trial protocol	In this arm no active medication was administered
Measure Participants	179	181
Count of Participants [Participants]	26 14.5%	37 20.4%

2. Primary Outcome

Title	The Number of Participants With Colchicine Side Effects
Description	The primary safety endpoint was the occurrence of side effects. Side effects monitored were mainly gastrointestinal effects (especially diarrhoea), alopecia, anorexia, hepatotoxicity, myotoxicity, and bone marrow toxicity.
Time Frame	From date of randomization until the date of discharge, assessed up to 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchicine	No Colchicine
Arm/Group Description	Colchicine 2 mg 12-24 hours prior to surgery and 1 mg 4 hours before or immediately after surgery and then continued at a dose of 0.5 mg twice daily until hospital discharge. Half the dose was given to patients weighing <70 kg or intolerant to the full dose. Colchicine: colchicine given as per trial protocol	In this arm no active medication was administered
Measure Participants	179	181
Number [participants]	55 30.7%	14 7.7%

Adverse Events

Arm/Group Title	Colchicine		No Colchicine
Arm/Group Description	Colchicine 2 mg 12-24 hours prior to surgery and 1 mg 4 hours before or immediately after surgery and then continued at a dose of 0.5 mg twice daily until hospital discharge. Half the dose was given to patients weighing <70 kg or intolerant to the full dose. Colchicine: colchicine given as per trial protocol		In this arm no active medication was administered
All Cause Mortality
	Colchicine		No Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Colchicine		No Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/179 (24.6%)		10/181 (5.5%)
Gastrointestinal disorders
Diarrhea	44/179 (24.6%)	44	10/181 (5.5%)	10
Other (Not Including Serious) Adverse Events
	Colchicine		No Colchicine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/179 (6.1%)		4/181 (2.2%)
Gastrointestinal disorders
Anorexia	11/179 (6.1%)	11	4/181 (2.2%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.