Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001345774
Ethics application status
Approved
Date submitted
14/10/2013
Date registered
9/12/2013
Date last updated
9/12/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Colchicine for the Primary Prevention of Atrial Fibrillation after Cardiac Surgery: A Double Blind Placebo Randomised Controlled Trial
Scientific title
Colchicine for the Primary Prevention of Atrial Fibrillation after Cardiac Surgery: A Double Blind Placebo Randomised Controlled Trial
Secondary ID [1] 283366 0
Nil
Universal Trial Number (UTN)
Trial acronym
Prevent AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative Atrial Fibrillation after Cardiac Surgery 290267 0
Condition category
Condition code
Cardiovascular 290655 290655 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Colchicine 0.5 mg oral twice daily for 7 days or until discharge (whichever occurs sooner).
Intervention code [1] 288093 0
Treatment: Drugs
Comparator / control treatment
Placebo (Cellulose) one capsule oral twice daily for 7 days or until discharge (whichever occurs sooner).
Control group
Placebo

Outcomes
Primary outcome [1] 290670 0
Incidence of postoperative atrial fibrillation: identified by continuous cardiac monitors on the wards and confirmed with a formal Electrocardiogram.
Timepoint [1] 290670 0
Discharge from acute hospital inpatient.
Secondary outcome [1] 305006 0
Duration of initial episode of postoperative atrial fibrillation: identified from the patients' nursing notes, which are based on continuous cardiac monitors.
Timepoint [1] 305006 0
Discharge from acute hospital inpatient
Secondary outcome [2] 305007 0
Number of episodes of postoperative atrial fibrillation: identified from the patients' nursing notes, which are based on continuous cardiac monitors.
Timepoint [2] 305007 0
Discharge from acute hospital inpatient
Secondary outcome [3] 305008 0
Cumulative duration of postoperative atrial fibrillation: identified from the patients' nursing notes, which are based on continuous cardiac monitors.
Timepoint [3] 305008 0
Discharge from acute hospital inpatient
Secondary outcome [4] 305009 0
Postoperative length of stay as acute hospital inpatient: assessed based on inpatient notes and hospital database.
Timepoint [4] 305009 0
Discharge from acute hospital inpatient
Secondary outcome [5] 305010 0
Incidence of Amiodarone use: identified from patients' drug charts
Timepoint [5] 305010 0
Discharge from acute hospital inpatient
Secondary outcome [6] 305011 0
Atrial fibrillation at time of discharge from acute hospital inpatient: identified from patients' observation charts
Timepoint [6] 305011 0
Discharge from acute hospital inpatient
Secondary outcome [7] 305012 0
Incidence of anti-coagulation use for treatment of postoperative atrial fibrillation: identified from patients' drug chart and discharge medication script.
Timepoint [7] 305012 0
Discharge from acute hospital inpatient
Secondary outcome [8] 305013 0
Incidence of Stroke (CVA/TIA) within 30 days of the operation: identified from the Australia and New Zealand Society of Cardiac and Thoracic Surgeons database sheet.
Timepoint [8] 305013 0
30 days
Secondary outcome [9] 305014 0
Representation or readmission to hospital for atrial fibrillation within 30 days: identified from the Australia and New Zealand Society of Cardiac and Thoracic Surgeons database sheet.
Timepoint [9] 305014 0
30 days

Eligibility
Key inclusion criteria
1. Isolated CABG
2. Isolated AVR
3. CABG and AVR
4. Able and willing to give informed consent
5. Able to comply with study procedures
6. No prior history of paroxysmal, persistent, permanent AF
7. In sinus rhythm at time of randomization
8. eGFR greater or equal to 35 ml/min at time of randomisation
9. Liver Transaminase (AST or ALT) less than 3 times the upper limit of normal at time of randomisation.
10. Extubated within 72 hours post-operatively and able to tolerate oral intake
11. Age older than 18 years
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known hypersensitivity to colchicine
2. Current treatment with colchicine
3. Known severe liver disease or current transaminases greater than three times the upper normal limit
4. Current eGFR less than 35 ml/min
5. Known myopathy or elevated baseline preoperative creatinine kinase (CK) not attributable to their medical condition
6. Known blood dyscrasias with abnormal preoperative Full Blood Examination (FBE) not attributable to their medical condition
7. Known severe gastrointestinal disease
8. Pregnant women, lactating women, or women of childbearing age.
9. Patients with known paroxysmal, persistent, or chronic AF
10. Patients extubated after 72 hours of their ICU admission post-operatively
11. Unable to tolerate oral intake

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Suitable patients will be identified on the wards and at consultant outpatient clinics of the Cardiothoracic Department and recruited over a period of 18 to 24 months. Ward patients who are suitable will be approached on the ward where they will be given the PICF and given enough time read the information and discuss with family members before consent is sought. Patients who are identified at consultant outpatient clinics will be given the PICF at the end of the consult, where they will have an opportunity to read and discuss the information with family members. They will then be followed up at preadmissions clinic for discussion of the trial and seeking of consent.
A preassigned randomisation schedule has been generated offsite and all medication bottles are labelled with a randomisation number. When the time comes for a patient to be randomised, they are given the next appropriate bottle of pre-randomised trial drug. Treating team, investigators, and participants are blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomly assigned in a 1:1 ratio of placebo and colchicine using a preassigned randomization schedule. The randomization will stratified for the type of surgery (CABG, AVR, CABG+AVR). A 24 hour code breaking facility, for unblinding the treatment allocation of an individual participant in case of an emergency is available.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The trial will be analyzed on an intention-to-treat basis with the primary outcome of whether the participant develops POAF or not (a dichotomous variable). Cox regression analysis will be used to estimate the relative risk reduction of POAF with colchicine. POAF-free survival after surgery will be evaluated in treatment and control groups using Kaplan-Meier survival curves and the log-rank test. Differences between treatment and placebo groups will be investigated using the Mann-Whitney test for continuous variables, and ?2 analysis for categorical variables. Treatment and placebo groups will be compared for baseline characteristics, primary and secondary outcomes:
Primary Outcome:
a) Incidence of POAF
Secondary Outcomes
a) Duration of AF
b) Recurrence of AF
c) Postoperative LOS
d) Representation for AF
e) Readmission for AF
f) Incidence of amiodarone use
g) Symptoms of toxicity
h) Adverse events
Sub-groups of our trial population will be analysed individually to investigate whether their outcomes differ from the whole trial population. These sub-groups will include but is not limited to:
a) CABG patient group
b) AVR patient group
c) Septuagenarian patients
d) Octogenarians patients
e) Patients who are extubated within 24 hours, 48 hours, and 72 hours may be analysed separately and compared.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/10/2013
Actual
21/10/2013
Date of last participant enrolment
Anticipated
26/12/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
520
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1581 0
Barwon Health - Geelong Hospital campus - Geelong

Funding & Sponsors
Funding source category [1] 288095 0
Charities/Societies/Foundations
Name [1] 288095 0
Heartbeat Geelong
Country [1] 288095 0
Australia
Funding source category [2] 288096 0
Charities/Societies/Foundations
Name [2] 288096 0
Australia and New Zealand Society of Cardiac and Thoracic Surgeons
Country [2] 288096 0
Australia
Primary sponsor type
Hospital
Name
Barwon Health - The Geelong Hospital
Address
Bellerine Street
Geelong, VIC 3220
Country
Australia
Secondary sponsor category [1] 286816 0
None
Name [1] 286816 0
Address [1] 286816 0
Country [1] 286816 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290019 0
Barwon Health Human Research and Ethics Committee
Ethics committee address [1] 290019 0
Kitchener House
Ryrie Street
Geelong, VIC 3220
Ethics committee country [1] 290019 0
Australia
Date submitted for ethics approval [1] 290019 0
Approval date [1] 290019 0
05/09/2013
Ethics approval number [1] 290019 0
12 / 169

Summary
Brief summary
The purpose of this study is to conduct a prospective double blind placebo randomized control trial to evaluate the effect of colchicine in preventing postoperative atrial fibrillation after cardiac surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43510 0
Dr Andrew Cheng
Address 43510 0
Dept. Cardiothoracic Surgery
Level 4, Kardinia House
Geelong Hospital
Bellerine Street
Geelong, VIC 3220
Country 43510 0
Australia
Phone 43510 0
+61 3 42151970
Fax 43510 0
Email 43510 0
[email protected]
Contact person for public queries
Name 43511 0
Ms Bernice Davies
Address 43511 0
Research Governance Officer
Kitchener House
Barwon Health - Geelong Hospital
Ryrie Street
Geelong, VIC 3220
Country 43511 0
Australia
Phone 43511 0
+61 3 42153372
Fax 43511 0
Email 43511 0
[email protected]
Contact person for scientific queries
Name 43512 0
Dr Andrew Cheng
Address 43512 0
Dept. Cardiothoracic Surgery
Level 4, Kardinia House
Geelong Hospital
Bellerine Street
Geelong, VIC 3220
Country 43512 0
Australia
Phone 43512 0
+61 3 42151970
Fax 43512 0
Email 43512 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIWhat’s Old is New Again – A Review of the Current Evidence of Colchicine in Cardiovascular Medicine2017https://doi.org/10.2174/1573403x12666161014094159
N.B. These documents automatically identified may not have been verified by the study sponsor.