Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000684820
Ethics application status
Approved
Date submitted
24/03/2021
Date registered
4/06/2021
Date last updated
4/06/2021
Date data sharing statement initially provided
4/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Sodium-Glucose Co-Transporter 2 inhibition prior to cardiac surgery and postoperative atrial fibrillation: a pilot randomised controlled trial
Scientific title
The effect of Sodium-Glucose Co-Transporter 2 inhibition prior to cardiac surgery on intraoperative electrophysiologic parameters and post-operative atrial fibrillation: a pilot randomised controlled trial
Secondary ID [1] 303752 0
Nil known
Universal Trial Number (UTN)
Trial acronym
DAPA Postop-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 321224 0
Cardiothoracic surgery 321279 0
Condition category
Condition code
Cardiovascular 319017 319017 0 0
Other cardiovascular diseases
Surgery 319551 319551 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomisation to dapagliflozin tablet, orally, 10mg daily for 1 month before and after cardiac surgery versus standard of care.
The total duration of dapagliflozin will be 2 months.
In further detail, total duration of treatment is 56 days. Treatment will be initiated 31 days prior to surgery and participants will receive 28 days of medication, then the medication will be withheld for 3 days prior to surgery, and then withheld on the day of the surgery. Treatment will be re-initiated post-operatively once the participant is eating and drinking normally, which is likely to be on the first postoperative day. Post operatively, the medication will be given for 28 days.
The pharmacy department will record the date of dispensing, and the number of tablets given. The pharmacy department also ask the participants to return unused medications, the number of unused tablets will be recorded on the study log.

Participants will be provided with an AliveCor cardiac monitor postoperatively, to transmit their cardiac traces twice a day postoperatively.

Participants taking dapagliflozin will be phoned every 2 weeks during the trial period to assess for side effects and answer questions, and 3 days before surgery to ensure cessation of medication.

Participants will be given a trial information booklet.

Cardiology consultants and fellows will be responsible for administering the trial, some elements over the phone and some in person visits; initial visit for consent/ collecting medication in person, phonecall after 2 weeks, another phonecall after 11 days, another phonecall 2 weeks post surgery, an in person visit 4 weeks after surgery.

Medication collection/ adherence will be documented by pharmacy department.
Intervention code [1] 320067 0
Treatment: Drugs
Comparator / control treatment
Control group is standard of care

The control group will receive standard of care, meaning that there will be no alterations to medications for participants in this group. Participants randomised to the control group (standard of care) will receive their usual medications, without the addition of a SGLT2 inhibitor. There will be no placebo tablet. Participants in the control group will they will not receive phonecalls at week 2 and 4 of study enrollment from study doctors as would the treatment group, as no intervention has been undertaken. At the time of surgery, both the control group and the treatment group will undergo the same intraprocedural electrophysiologic assessment. Post-operatively, both the control group and the treatment group will be asked to submit electronic traces of their heart rhythm twice a day, and if they experience symptoms, for one month following their surgery.
Control group
Active

Outcomes
Primary outcome [1] 326922 0
Proportion of electrograms from the endocardial surface and epicardial surface showing endo-epicardial dissociation, as measured during the intra-operative electrophysiology study (using the BARD on wheels). There will be no pre- or post-operative electrophysiology studies.

In simple terms, dissociation means there is a substantial timing difference in the arrival times of electrical wavefronts between opposed nearest neighbour electrodes on the endocardial and epicardial surfaces.

Instruments
- HD Grid catheters x2 per patient (St Jude Medical) for performance of intraoperative electrophysiology study
- BARD on wheels for performance of electrophysiology study
Timepoint [1] 326922 0
Measured during cardiac surgery, prior to the commencement of cardiopulmonary bypass. No repeat recordings during cardiac surgery.
Primary outcome [2] 327404 0
Atrial fibrillation burden over the 1 month postoperative period. Part 1: Inpatient stay.

During the hospital admission (likely to be approximately the first postoperative week), inpatient cardiac monitoring will be reviewed daily to assess the number of hours in atrial fibrillation.
Timepoint [2] 327404 0
Measured daily during the inpatient postoperative stay (estimated to be 1-2 weeks), length of stay determined by clinical course and inpatient team
Primary outcome [3] 327405 0
Atrial fibrillation burden over the 1 month postoperative period. Part 2: Following hospital discharge.

Once inpatient cardiac monitoring is removed (at the discretion of the treating team), the patient will be transitioned to AliveCor monitoring of their cardiac rhythm twice daily. Participants will be asked to return two traces each day of their heart rhythm, and additional traces if they experience symptoms concerning for atrial fibrillation, via their AliveCor device and compatible smartphone. The percentage of traces showing atrial fibrillation will be recorded and measured.
Timepoint [3] 327405 0
Measured daily over the 1 month post surgery.
Secondary outcome [1] 393146 0
Conduction velocity measured in the direction of maximum vector amplitude.

Tools:
- HD Grid catheters x2 per patient (St Jude Medical) for performance of intraoperative electrophysiology study
- BARD on wheels for performance of intraoperative electrophysiology study
Timepoint [1] 393146 0
Measured during cardiac surgery, prior to the commencement of cardiopulmonary bypass. No repeat recordings during cardiac surgery.
Secondary outcome [2] 394986 0
Difference in atrial effective refractory period

Tools:
- HD Grid catheters x2 per patient (St Jude Medical) for performance of intraoperative electrophysiology study
- BARD on wheels for performance of intraoperative electrophysiology study
Timepoint [2] 394986 0
Measured during cardiac surgery, prior to the commencement of cardiopulmonary bypass. No repeat recordings during cardiac surgery.
Secondary outcome [3] 394987 0
Proportion of fractionated (high entropy) electrograms

Tools:
- HD Grid catheters x2 per patient (St Jude Medical) for performance of intraoperative electrophysiology study
- BARD on wheels for performance of intraoperative electrophysiology study
Timepoint [3] 394987 0
Measured during cardiac surgery, prior to the commencement of cardiopulmonary bypass. No repeat recordings during cardiac surgery.
Secondary outcome [4] 394988 0
Proportion of patients with inducible atrial fibrillation

Tools:
- HD Grid catheters x2 per patient (St Jude Medical) for performance of intraoperative electrophysiology study
- BARD on wheels for performance of intraoperative electrophysiology study
Timepoint [4] 394988 0
Measured during cardiac surgery, prior to the commencement of cardiopulmonary bypass. No repeat recordings during cardiac surgery.
Secondary outcome [5] 394989 0
Differences in renewal rate constants of rotor formation and destruction during induced atrial fibrillation episodes.

We will measure the renewal rate constant of rotor formation and the renewal rate constant of rotor destruction and calculate the difference between formation and destruction.

Tools: - HD Grid catheters x2 per patient (St Jude Medical) for performance of intraoperative electrophysiology study
- BARD on wheels for performance of electrophysiology study
Timepoint [5] 394989 0
Measured during cardiac surgery, prior to the commencement of cardiopulmonary bypass. No repeat recordings during cardiac surgery.

Eligibility
Key inclusion criteria
Participants undergoing planned elective cardiac surgery (> 1 month prior to surgical date at time of enrolment)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are unable or unwilling to provide consent.
Patients who do not have access to a smartphone.
Patients who do not consent to study coordinator discussing their involvement with their GP.
Contraindications to SGLT2 commencement; patients already taking SGLT2 inhibitors, history of impaired kidney function (eGFR <45mL/min/1.73m2), Child –Pugh C cirrhosis, pregnancy, breastfeeding, symptomatic hypotension/ systolic blood pressure <100mmHg, type 1 diabetes mellitus, or previous SGLT2 intolerance or allergy, in line with current published contraindications to therapy.

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
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
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size Determination: Parameswaran et al., in 2020, identified a 22% probability of endo-epicardial dissociated electrograms from 9,218 electrograms assessed in n=16 patients, using a similar electrophysiologic protocol. Power calculations were performed for logistic regression for a 10% change of in the probability of endo-epi dissociated electrograms, with alpha=0.025, 1-beta=0.90, in a logistic regression model including a squared correlation with 4 predictors of 0.4. Using this approach, n=6436 electrograms are required in each arm, suggesting n=8 patients per randomised arm will be sufficient to identify a significant difference in proportion of endo-epicardial dissociated electrograms.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/06/2021
Actual
Date of last participant enrolment
Anticipated
2/05/2022
Actual
Date of last data collection
Anticipated
4/07/2022
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 18983 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 33490 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 308160 0
University
Name [1] 308160 0
Flinders University
Country [1] 308160 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Flinders University
Sturt Road
Bedford Park, South Australia 5042
Country
Australia
Secondary sponsor category [1] 308947 0
None
Name [1] 308947 0
Address [1] 308947 0
Country [1] 308947 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308146 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 308146 0
Flinders Medical Centre, Level 6, Ward 6C, Room 6A219 level 6
Flinders Drive, Bedford Park, SA 5042
Ethics committee country [1] 308146 0
Australia
Date submitted for ethics approval [1] 308146 0
Approval date [1] 308146 0
10/03/2021
Ethics approval number [1] 308146 0

Summary
Brief summary
Post-operative atrial fibrillation is a heart rhythm disorder that is a major clinical problem, affecting 15-30% of patients undergoing cardiac surgery. It is associated with high rates of stroke, and increased mortality. Post-operative atrial fibrillation is thought to be caused by abnormalities in the physiological function of the atrium around the time of surgery. The current application is for a pilot open-label randomised controlled trial assessing the impact of sodium-glucose co-transporter 2 inhibitor pre-treatment on cardiac electrophysiology studies performed during cardiac surgery in 16 patients. The rationale for the study is that this medication has been shown in a very large randomised controlled trial (Wiviott SD et al. NEJM 2019 "DECLARE-TIMI 58" trial) to decrease incident atrial fibrillation by 19%. We therefore reason that these medications may potentially mediate this effect.
The aim of the current study is to determine if pre-treatment will improve the electrical function of the atrium, or change the rates of postoperative atrial fibrillation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109690 0
A/Prof Anand Ganesan
Address 109690 0
Department of Cardiology, Level 6, Flinders Medical Centre. Flinders Drive, Bedford Park SA 5042.
Country 109690 0
Australia
Phone 109690 0
+61 08 8204 5619
Fax 109690 0
Email 109690 0
[email protected]
Contact person for public queries
Name 109691 0
Dr Kathryn Tiver
Address 109691 0
Department of Cardiology, Level 6, Flinders Medical Centre. Flinders Drive, Bedford Park SA 5042.
Country 109691 0
Australia
Phone 109691 0
+61 08 82045836
Fax 109691 0
Email 109691 0
[email protected]
Contact person for scientific queries
Name 109692 0
A/Prof Anand Ganesan
Address 109692 0
Department of Cardiology, Level 6, Flinders Medical Centre. Flinders Drive, Bedford Park SA 5042.
Country 109692 0
Australia
Phone 109692 0
+61 08 8204 5619
Fax 109692 0
Email 109692 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.