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Trial registered on ANZCTR


Registration number
ACTRN12616000256471
Ethics application status
Approved
Date submitted
22/02/2016
Date registered
24/02/2016
Date last updated
6/09/2019
Date data sharing statement initially provided
8/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring the link between alcohol and atrial fibrillation recurrence: a multicentre randomised controlled trial (ETOH-AF)
Scientific title
Exploring the link between alcohol and atrial fibrillation recurrence: a multicentre randomised controlled trial (ETOH-AF)
Secondary ID [1] 288588 0
Nil known
Universal Trial Number (UTN)
U1111-1179-9127
Trial acronym
ETOH-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 297725 0
Atrial flutter 297726 0
Alcohol abuse 297727 0
Cardiomyopathy 297728 0
Hypertension 297729 0
Obstructive sleep apnoea 297730 0
Condition category
Condition code
Cardiovascular 297912 297912 0 0
Other cardiovascular diseases
Public Health 297913 297913 0 0
Health promotion/education

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Alcohol abstinence: All patients in this arm will be encouraged and counselled to abstain completely from all forms of alcohol for a 12-month period. They will have a one-on-one 15-minute session with a specialist physician at 0,3,6,9 and 12 months, as would occur in routine clinical practice (note patients with alcohol dependence are excluded from the study). Attendance will be recorded. They will be provided written advice and links to online resources to assist them. Patients with initial difficulty in abstaining from alcohol will be referred to a clinician with specialized expertise in alcohol-related counselling, brief intervention and anti-craving therapy. Compliance will be monitored by weekly alcohol consumption diaries, weekly phone calls, as well as random urine testing for alcohol metabolites (urine ETG, pending funding).

Patients in both arms will have a 1 month run-in phase prior to being formally randomized - they will be required to submit weekly alcohol diaries. This will assess their compliance and also ensure they meet the inclusion criteria for alcohol intake.
Intervention code [1] 293985 0
Lifestyle
Intervention code [2] 294007 0
Treatment: Other
Intervention code [3] 294008 0
Prevention
Comparator / control treatment
Control arm: Patients in this control group will be advised they can continue their usual alcohol consumption. However, they will be provided written & verbal information about recommended safe levels of drinking and encouraged to have regular follow-up with their usual treating clinician.

Patients in both arms will have a 1 month run-in phase prior to being formally randomized - they will be required to submit weekly alcohol diaries. This will assess their compliance and also ensure they meet the inclusion criteria for alcohol intake.
Control group
Active

Outcomes
Primary outcome [1] 297432 0
Atrial fibrillation / flutter (AF) burden - percentage of time spent in AF during the follow-up period (as assessed by either 3-monthly 7-day Holter monitor + symptom review with ECG, loop recorder or dual-chamber pacemaker).
Timepoint [1] 297432 0
From start of intervention to 6 months later
Primary outcome [2] 297433 0
Time to first AF recurrence (by either Holter monitor, loop recorder, dual-chamber pacemaker, or ECG during symptoms)
Timepoint [2] 297433 0
Within the first 6 months from start of intervention (after a two week blanking period)
Secondary outcome [1] 321029 0
Hospitalisations for AF (by review of medical records and ECGs during hospitalisation)
Timepoint [1] 321029 0
Within the first 6 months from start of intervention.
Secondary outcome [2] 321030 0
Blood pressure (over brachial artery, measured by sphygmomanometer)
Timepoint [2] 321030 0
At 0 and 6 months.
Secondary outcome [3] 321031 0
Weight (measured by digital scales)
Timepoint [3] 321031 0
At 0 and 6 months.
Secondary outcome [4] 321033 0
Quality of life, as assessed by SF-36 Quality of Life Questionnaire
Timepoint [4] 321033 0
At 0 and 6 months.
Secondary outcome [5] 321034 0
Depression, as assessed by % with Beck depression score > 10
Timepoint [5] 321034 0
At 0 and 6 months.
Secondary outcome [6] 321040 0
Cardiac MRI LV end-diastolic volume index (LVEDVI) (optional sub study, pending funding)


Timepoint [6] 321040 0
0 and 6 months
Secondary outcome [7] 321041 0
Number of AF recurrences (as measured by either Holter monitor, loop recorder, dual-chamber pacemaker, or ECG during symptoms)
Timepoint [7] 321041 0
In first 6 months from start of intervention.
Secondary outcome [8] 321103 0
Cardiac MRI LV mass index (optional sub study, pending funding)
Timepoint [8] 321103 0
0 and 6 months
Secondary outcome [9] 321104 0
Cardiac MRI LV ejection fraction (optional sub study, pending funding)
Timepoint [9] 321104 0
0 and 6 months
Secondary outcome [10] 321107 0
Cardiac MRI LV tissue characterisation (optional sub study, pending funding) using T1 mapping, STIR, late Gadolinium enhancement
Timepoint [10] 321107 0
0 and 6 months
Secondary outcome [11] 321108 0
Cardiac MRI left atrial function - using strain, LA ejection fraction, LA passive emptying fraction (optional sub study, pending funding)
Timepoint [11] 321108 0
0 and 6 months
Secondary outcome [12] 321109 0
Cardiac MRI left atrial volume (optional sub study, pending funding)
Timepoint [12] 321109 0
0 and 6 months
Secondary outcome [13] 321110 0
Cardiac MRI left atrial tissue characterisation with T1 mapping (optional sub study, pending funding)
Timepoint [13] 321110 0
0 and 6 months
Secondary outcome [14] 321111 0
Cardiac MRI left atrial area (optional sub study, pending funding)
Timepoint [14] 321111 0
0 and 6 months
Secondary outcome [15] 336075 0
Change in AF burden – comparison between percentage of time spent in AF during the follow-up period (as assessed by either 3-monthly 7-day Holter monitor + symptom review with ECG, loop recorder or dual-chamber pacemaker) and baseline burden
Timepoint [15] 336075 0
Comparison between 0 & 6 months
Secondary outcome [16] 336968 0
European Heart Rhythm Association (EHRA) score for AF-related symptoms
Timepoint [16] 336968 0
0 and 6 months

Eligibility
Key inclusion criteria
- Paroxysmal AF (atrial fibrillation and/or flutter) with minimum 2 episodes in the last 6 months or persistent AF requiring direct cardioversion
- Average alcohol intake at least 10 standard drinks per week (120 g/week).

To be eligible for the sub-study (ABSTAIN-PVI), patients will need to have had a previous pulmonary vein isolation (AF ablation) procedure (in addition to the above criteria).
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of alcohol dependence (as determined by CAGE & AUDIT-C questionnaires)
- Presence of significant psychiatric comorbidity or cognitive impairment
- Permanent AF (where sinus rhythm cannot be restored)
- Advanced heart failure, as defined by left ventricular ejection fraction < 35%.
- Limited life expectancy (less than 24 months) due to co-morbid non-cardiac illness, including liver failure, end-stage renal disease or advanced malignancy.


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
There will be initial concealment of allocation from study investigators (using central randomisation by a computer)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
For ETOH-AF, the sample size calculation for the primary endpoint of time to AF recurrence assumes an annual recurrence rate of 30% based on preliminary data. To detect a minimum absolute difference in recurrence of 20% between groups, we will need to enrol 70 patients in each group to provide a power of 0.8 at an alpha value of 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2016
Actual
7/03/2016
Date of last participant enrolment
Anticipated
2/04/2018
Actual
20/02/2018
Date of last data collection
Anticipated
20/08/2018
Actual
20/08/2018
Sample size
Target
140
Accrual to date
Final
140
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5307 0
The Alfred - Prahran
Recruitment hospital [2] 5308 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 5309 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [4] 5310 0
Western Hospital - Footscray
Recruitment hospital [5] 5311 0
Sunshine Hospital - St Albans
Recruitment hospital [6] 5312 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [7] 5313 0
Melbourne Private Hospital - Parkville
Recruitment hospital [8] 5314 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 12773 0
3181 - Prahran
Recruitment postcode(s) [2] 12774 0
3168 - Clayton
Recruitment postcode(s) [3] 12775 0
3052 - Parkville
Recruitment postcode(s) [4] 12776 0
3084 - Heidelberg
Recruitment postcode(s) [5] 12777 0
3011 - Footscray
Recruitment postcode(s) [6] 12778 0
3020 - Sunshine
Recruitment postcode(s) [7] 12779 0
3144 - Malvern

Funding & Sponsors
Funding source category [1] 292936 0
Self funded/Unfunded
Name [1] 292936 0
Prof Peter Kistler
Country [1] 292936 0
Australia
Primary sponsor type
Individual
Name
Prof Peter Kistler
Address
Heart Centre, Alfred Hospital, Commercial Rd, Prahran, Vic, 3181
Country
Australia
Secondary sponsor category [1] 291700 0
Individual
Name [1] 291700 0
Dr Aleksandr Voskoboinik
Address [1] 291700 0
Heart Centre, Alfred Hospital, Commercial Rd, Prahran, Vic, 3181
Country [1] 291700 0
Australia
Other collaborator category [1] 278843 0
Individual
Name [1] 278843 0
Prof Jonathan Kalman
Address [1] 278843 0
Department of Cardiology, Royal Melbourne Hospital, Grattan St, Parkville, Vic, 3052
Country [1] 278843 0
Australia
Other collaborator category [2] 278844 0
Individual
Name [2] 278844 0
Dr Emily Kotschet
Address [2] 278844 0
Department of Cardiology, Monash Medical Centre, Clayton Rd, Clayton, Vic, 3168
Country [2] 278844 0
Australia
Other collaborator category [3] 278845 0
Individual
Name [3] 278845 0
Dr Michael Wong
Address [3] 278845 0
Department of Cardiology, Western Hospital, Gordon St, Footscray, Vic, 3011
Country [3] 278845 0
Australia
Other collaborator category [4] 278846 0
Individual
Name [4] 278846 0
A/Prof Omar Farouque
Address [4] 278846 0
Department of Cardiology, Austin Hospital, Studley Rd, Heidelberg, Vic, 3084
Country [4] 278846 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294441 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 294441 0
Alfred Hospital, Commercial Rd, Prahran, Vic, 3181
Ethics committee country [1] 294441 0
Australia
Date submitted for ethics approval [1] 294441 0
17/12/2015
Approval date [1] 294441 0
08/01/2016
Ethics approval number [1] 294441 0
HREC/15/Alfred/84

Summary
Brief summary
ETOH-AF trial:
While the association between binge drinking and atrial tachyarrhythmias is well-established, even moderate alcohol consumption has recently been identified as a significant risk factor for atrial fibrillation and/or flutter (AF) in a dose-dependent manner. To date, there have been no randomised-controlled trials looking at the impact of alcohol abstinence on AF outcomes. Moreover, we are keen to look at the overall effects of alcohol abstinence on other cardiovascular outcomes (inc. blood pressure, cardiac structure and function, sleep apnoea) and non-cardiovascular outcomes (inc. quality of life, mood). We hypothesise that alcohol abstinence will reduce AF recurrences, AF burden, AF symptoms and AF hospitalisations, as well as resulting in reductions in LV size, LA size, sleep apnoea parameters and blood pressure, and improvements in LA & LV function, mood and quality of life.

We intend to recruit at least 140 patients and randomise them to either an alcohol Abstinence or Control arm, and follow them up for 12 months (with a 1 month run-in phase prior). Alcohol consumption in both arms will be monitored using weekly alcohol diaries, urine ETG (pending funding) and blood tests (inc. MCV, GGT).

Monitoring for AF recurrences will occur by either:
(i) Insertion of an implantable loop recorder OR
(ii) Wearing a 7-day Holter monitor every 3 months +/- ECG transmission using the AliveECG smartphone app (if available) +/- ECG during symptoms of AF
(iii) Interrogation of permanent pacemakers/defibrillators every 3 months in those with pre-existing dual chamber devices.

Baseline and follow-up data collected includes:
12-lead ECG - 0 and 12 months.
Blood pressure and weight - 0,3,6,9,12 months.
Sleep study - 0 and 12 months.
Basic bloods (lipids, glucose, FBE, UEC, LFT, BNP) - 0,6,12 months.
Transthoracic echocardiogram (inc. LV size & EF, LA size, LA strain) - 0 and 12 months.
AF symptom severity questionnaire (AFSS) & Medical questionnaire - 0,3,6,9,12 months.
Mood & quality of life questionnaires - 0 & 12 months.
Cardiac MRI substudy (pending funding) - 0 and 6-12 months.

We will also be looking at a subgroup of patients who have had a previous pulmonary vein isolation (ABSTAIN-PVI substudy) to determine whether alcohol abstinence is beneficial in this sub-population. The trial protocol is unchanged (inc. outcomes) for these patients.
Trial website
N/A
Trial related presentations / publications
Nil to date
Public notes
If you have atrial fibrillation or flutter and consume more than 10 drinks of alcohol per week, and are keen to enrol in a trial looking at the effects of alcohol abstinence, please email [email protected]

Contacts
Principal investigator
Name 63722 0
Prof Peter Kistler
Address 63722 0
Heart Centre, Alfred Hospital, Commercial Rd, Prahran, Vic, 3181
Country 63722 0
Australia
Phone 63722 0
+61 3 8532 1427
Fax 63722 0
Email 63722 0
[email protected]
Contact person for public queries
Name 63723 0
Aleksandr Voskoboinik
Address 63723 0
Heart Centre, Alfred Hospital, Commercial Rd, Prahran, Vic, 3181
Country 63723 0
Australia
Phone 63723 0
+61 3 90762000
Fax 63723 0
+61 3 80800747
Email 63723 0
[email protected]
Contact person for scientific queries
Name 63724 0
Aleksandr Voskoboinik
Address 63724 0
Heart Centre, Alfred Hospital, Commercial Rd, Prahran, Vic.
Country 63724 0
Australia
Phone 63724 0
+61 3 90762000
Fax 63724 0
+61 3 80800747
Email 63724 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Spreadsheet of de-identified data with primary and secondary endpoints
When will data be available (start and end dates)?
From 1st January 2020 until 1st January 2022
Available to whom?
Researchers with a suitable research plan / proposal.
Available for what types of analyses?
Meta-analyses and systematic reviews
How or where can data be obtained?
By contacting Dr Voskoboinik - email: [email protected]


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
EmbaseAlcohol Abstinence in Drinkers with Atrial Fibrillation.2020https://dx.doi.org/10.1056/NEJMoa1817591
N.B. These documents automatically identified may not have been verified by the study sponsor.