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Trial registered on ANZCTR


Registration number
ACTRN12621000208808
Ethics application status
Approved
Date submitted
22/12/2020
Date registered
26/02/2021
Date last updated
12/05/2022
Date data sharing statement initially provided
26/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of SGLT2 Inhibition With Empagliflozin on Atrial Fibrillation Severity (SWEET-AF)
Scientific title
Effect of SGLT2 Inhibition With Empagliflozin on Atrial Fibrillation Severity in overweight adults (SWEET-AF)
Secondary ID [1] 303050 0
None
Universal Trial Number (UTN)
Trial acronym
SWEET-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 320118 0
Condition category
Condition code
Cardiovascular 318058 318058 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A total of 300 individuals with symptomatic paroxysmal or persistent AF will be randomised in 1:1 ratio to Empagliflozin or Placebo for a total of 12 months.
Empagliflozin tablets and respective placebo tablets will be identical in size, colour, smell and taste. The bottles of study medication will be labelled with unique identification numbers.
Participants will take one tablet daily. The dose of Empagliflozin is 10 miligrams.
Medication adherence will be ascertained by drug tablet return.
Intervention code [1] 319336 0
Treatment: Drugs
Comparator / control treatment
Microcrystalline cellulose, oral tablet
Control group
Placebo

Outcomes
Primary outcome [1] 326052 0
Change in AF symptomatology assessed via the AF symptom severity score (AFSS)
Timepoint [1] 326052 0
3, 6, 9 and 12 months post randomisation (primary timepoint
Primary outcome [2] 326053 0
Change in AF burden assessed via 7-day Holter monitor
Timepoint [2] 326053 0
3, 6, 9 and 12 months post randomisation (primary timepoint
Primary outcome [3] 326349 0
Change in the AF effect on quality of life score (AFQET)
Timepoint [3] 326349 0
3, 6, 9 and 12 months post randomisation (primary timepoint
Secondary outcome [1] 389992 0
Change in adiposity assessed through BMI
Timepoint [1] 389992 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [2] 389993 0
Change in glycaemia assessed through bloods sample measuring glucose and glycosylated haemoglobin
Timepoint [2] 389993 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [3] 389994 0
Changes in blood pressure using a blood pressure cuff
Timepoint [3] 389994 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [4] 389995 0
A composite outcome of change in cardiac structure and function assessed using transthoracic echocardiography and cardiovascular magnetic resonance imaging (CMR).
Timepoint [4] 389995 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [5] 389996 0
Composite outcome of change in exercise capacity assessed using the six-minute walk test and cardiopulmonary exercise testing (CPET)
Timepoint [5] 389996 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [6] 389997 0
Clinical events including cardiac and all cause-death, myocardial infarction, heart failure, stroke, unplanned hospitalisation, cardiac procedure assessed from medical records/patient reporting
Timepoint [6] 389997 0
12 months post randomisation
Secondary outcome [7] 389998 0
Retinal microvasculature assessed using optical coherence tomography angiography
Timepoint [7] 389998 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [8] 389999 0
Adverse drug reactions (confirmed hypoglycaemia, urinary tract infections, genital infection, volume depletion, acute kidney injury, bone fracture, diabetic ketoacidosis, thromboembolic events, amputation assessed via patient reporting/medical records.
Timepoint [8] 389999 0
12 months post randomisation
Secondary outcome [9] 390000 0
Medication compliance/discontinuation assessed using tablet return
Timepoint [9] 390000 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [10] 390031 0
Change in albumin creatinine ratio assessed through urinary samples
Timepoint [10] 390031 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [11] 391113 0
Change in waist circumference. Waist circumference will be determined using a measuring tape positioned at the high point of the iliac crest
Timepoint [11] 391113 0
12 months
Secondary outcome [12] 391114 0
Waist-to-hip ratio,
Waist circumference will be determined using a measuring tape positioned at the high point of the iliac crest. Hip circumference will be determined using a measuring tape positioned at the trochanter level. Waist-to-hip ratio will subsequently be calculated using these two measurements
Timepoint [12] 391114 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [13] 391115 0
Change in pericardial fat through MRI
Timepoint [13] 391115 0
3, 6, 9 and 12 months post randomisation
Secondary outcome [14] 391116 0
Change in subcutaneous fat through MRI
Timepoint [14] 391116 0
12 months

Eligibility
Key inclusion criteria
• At least 18 years of age
• Symptomatic paroxysmal or persistent AF (in sinus rhythm at time of enrolment)
• Body mass index (BMI) > 27
• NB: A history of diabetes is not required for inclusion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Current or prior use of SGLT2 inhibitor
• Not on stable glucose-lowering regimen for 12 weeks if diabetic
• Estimated glomerular filtration rate < 30ml/min/1.73m2
• Acute, decompensated heart failure
• Women pregnant, nursing, or who plan to become pregnant during trial period
• Contraindication to CMR (implanted cardiac devices, cochlear implants, intracranial metallic implants and claustrophobia).
• Inability to provide informed consent

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated web-based randomisation schedule
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Based on previously published studies and weight loss data from SGLT2 trials, we anticipate that randomisation of 250 patients will provide robust statistical power to detect plausible and clinically relevant proportional reductions in 7-day AF burden of 2.5 hours with 80% power and 2-sided alpha level of 0.05. Power calculation assumptions include an estimated 2.5 kg weight loss with Empagliflozin compared to placebo corresponding to an estimated 2.5 hours reduction in weekly AF burden with Empagliflozin compared to placebo. Past studies indicate a comparable reduction in 7-day AF burden results in clinical improvements in AF symptoms and cardiac structure. Taking the above into account, we plan to recruit 300 patients in total (150 patients per group) to allow for a 20% discontinuation rate. During the trial, blinded AF burden (i.e. both groups combined) will be monitored, and if AF burden is significantly less than anticipated as outlined above, the steering committee will have the option of increasing the sample size, or changing the eligibility criteria to recruit higher-risk patients (for example, individuals with greater AF burden or symptom scores), to maximise the ability to detect differences. Similarly, monitoring of dropout rates will be undertaken and, if substantially greater than anticipated, the above options are also available to the steering committee to increase statistical power if desired.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2021
Actual
15/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
30
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 18240 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 32304 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 307459 0
Charities/Societies/Foundations
Name [1] 307459 0
The Hospital Research Foundation
Country [1] 307459 0
Australia
Funding source category [2] 307470 0
Charities/Societies/Foundations
Name [2] 307470 0
National Heart Foundation
Country [2] 307470 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
North Terrace, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 308132 0
None
Name [1] 308132 0
Address [1] 308132 0
Country [1] 308132 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307536 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 307536 0
Royal Adelaide Hospital, Port Road Adelaide, SA 5000
Ethics committee country [1] 307536 0
Australia
Date submitted for ethics approval [1] 307536 0
20/05/2020
Approval date [1] 307536 0
14/07/2020
Ethics approval number [1] 307536 0
13247

Summary
Brief summary
Atrial fibrillation (AF) is the most common arrhythmia in Australia and confers a significant risk of stroke, heart failure and death. Furthermore, patients with symptomatic AF represent a growing burden on the Australian healthcare system. In view of this epidemic, new approaches to preventing and managing the symptoms and complications of AF are required.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are new class of medications designed with diabetes in mind via the renal excretion of glucose. However, in addition to lowering blood glucose, these agents also appear to have significant pleiotropic effects on multiple cardiometabolic factors that are associated with AF.There is strong rationale for the potential benefit of SGLT2 inhibition in patients with AF. However, this class of medications have not been previously tested in these individuals.

This study is a Phase II, investigator-initiated, multicenter, randomised controlled trial, investigating the use of Empagliflozin, a SGLT2 inhibitor in patients with AF. It is anticipated that SGLT2 inhibition with Empagliflozin will significantly reduce AF symptoms and arrhythmia burden.

A total of 300 participants with symptomatic paroxysmal or persistent AF will be recruited and randomised in 1:1 ratio to Empagliflozin or Placebo. Participants will attend follow up clinic visits every 3 months for a 1-year period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107586 0
Dr Christopher Wong
Address 107586 0
Royal Adelaide Hospital
Port Road, Adelaide SA 5000
Country 107586 0
Australia
Phone 107586 0
+610883139012
Fax 107586 0
Email 107586 0
[email protected]
Contact person for public queries
Name 107587 0
Ellen Lyrtzis
Address 107587 0
Cardiovascular Centre,
62 Beulah Road, Norwood SA 5067
Country 107587 0
Australia
Phone 107587 0
+610883139000
Fax 107587 0
Email 107587 0
[email protected]
Contact person for scientific queries
Name 107588 0
Christopher Wong
Address 107588 0
Royal Adelaide Hospital
Port Road, Adelaide, SA 5000
Country 107588 0
Australia
Phone 107588 0
+610883139000
Fax 107588 0
Email 107588 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.