Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000227695p
Ethics application status
Submitted, not yet approved
Date submitted
4/08/2022
Date registered
3/03/2023
Date last updated
3/03/2023
Date data sharing statement initially provided
3/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The SAD-AF trial: a study of escitalopram (a selective serotonin reuptake inhibitor, SSRI) antidepressant vs placebo in patients with atrial fibrillation (AF) and depression, on AF-related quality of life
Scientific title
Selective serotonin reuptake inhibitors And Depression in Atrial Fibrillation: the SAD-AF randomised controlled trial of escitalopram vs placebo in patients with AF and depression evaluating AF-related quality of life
Secondary ID [1] 307714 0
2022.260
Universal Trial Number (UTN)
Trial acronym
SAD-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation 327275 0
major depressive disorder 327276 0
Condition category
Condition code
Cardiovascular 324407 324407 0 0
Other cardiovascular diseases
Mental Health 324408 324408 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral administration of escitalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant versus placebo. There are two arms: Arm 1 = escitalopram 10mg once daily with option to titrate up to 20mg once daily, Duration of administration = 12 months.

Materials: baseline, 6-month and 12-month questionnaires as below
1. PHQ-9 questionnaire for depression symptoms https://med.stanford.edu/fastlab/research/imapp/msrs/_jcr_content/main/accordion/accordion_content3/download_256324296/file.res/PHQ9%20id%20date%2008.03.pdf

2. AFEQT (AF Effect on Quality of Life)
http://www.afeqt.org/files/AFEQT_Questionnaire.pdf

3. SF-36 (Short-form 36 for general quality of life)
https://clinmedjournals.org/articles/jmdt/jmdt-2-023-figure-1.pdf

ECG monitoring: AliveCor phone app (twice daily ECGs) or conventional 3-lead 7-day Holter monitoring
Escitalopram dosing may be tailored to an increase from 10mg daily to 20mg daily at the discretion of the reviewing medical practitioner at any of the visits.

Provider: medical doctor for prescription and assessment, central clinical trials pharmacy team for medication dispensing, clinical nurse specialist for follow-up visits.

Adherence assessment: assessed by pharmacy dispensing records and pill counts by pharmacy personnel.
Intervention code [1] 324189 0
Treatment: Drugs
Comparator / control treatment
Arm 2 = placebo with corresponding uptitration option. This is composed from a blend of Pregelatinised Maize Starch and Maize Starch. Patients receiving placebo will also have a corresponding uptitration option, where their dosing may be tailored to an increase from 10mg daily to 20mg daily at the discretion of the reviewing medical practitioner at any of the visits.
Control group
Placebo

Outcomes
Primary outcome [1] 332221 0
Change in AF Effect on Quality of Life (AFEQT) score
Timepoint [1] 332221 0
AF related quality of life, measured by patient-completed AFEQT (AF effect on quality of life) questionnaire. This is measured at baseline, 3 months, 6 months and 12 months (primary timepoint) after intervention commencement.
Secondary outcome [1] 412595 0
AF burden
If using Alivecor phone app: Assessed as a percentage of all available tracings over 12-month period

If using conventional Holter 7-day monitoring: Assessed as a percentage of all available tracings over timepoints of 3, 6, 9 and 12 months

If using pre-existing cardiac device interrogation: assessed as percentage recorded by the device over the 6 month and 12 month interrogation period
Timepoint [1] 412595 0
If using Alivecor phone app: 6 months and 12 months after intervention commencement

If using conventional Holter 7-day monitoring: 6 months and 12 months after intervention commencement

If using pre-existing cardiac device interrogation: 6 months and 12 months after intervention commencement
Secondary outcome [2] 412596 0
Time to recurrence of AF (days) assessed by ECG monitoring by any one of the following methods:
1) Alivecor Phone app
2) Conventional 7-day Holter monitoring
3) Pre-existing cardiac device interrogation
Timepoint [2] 412596 0
Measured from 2 month time point to the first recorded episode of AF, for a maximum period of 12 months post-intervention commencement.
If in AF at 2 months, time is listed as 60 days.
Secondary outcome [3] 412597 0
General quality of life using SF-36 score
Timepoint [3] 412597 0
Baseline, 6 months, 12 months post intervention commencement
Secondary outcome [4] 412598 0
Number of AF hospitalisations via data linkage to electronic medical records
Timepoint [4] 412598 0
6 months, 12 months post-intervention commencement
Secondary outcome [5] 412599 0
Depressive symptoms as measured by PHQ-9
Timepoint [5] 412599 0
Baseline, 6 months, 12 months post-intervention commencement

Eligibility
Key inclusion criteria
• Age greater than or equals to 18 years old
• Paroxysmal AF (atrial fibrillation and/or flutter), with minimum 2 episodes in the last 6 months or persistent AF requiring direct cardioversion
• Score of >=5/27 on the PHQ-9.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Presence of significant psychiatric comorbidity where it is considered unsafe to alter current treatment regimen
• Presence of significant cognitive impairment
• Inability or unwillingness to provide informed consent
• Permanent AF (where sinus rhythm cannot be restored)
• Advanced heart failure, as defined by left ventricular ejection fraction < 35%.
• Severe renal impairment defined as creatinine clearance <=30ml/min
• Hepatic impairment defined as the presence of cirrhosis
• Life expectancy <= 24 months due to co-morbid non-cardiac illness, including liver failure, end-stage renal disease or advanced malignancy.
• Age > 85 years-old
• Critically unwell patients.

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)
Simple randomisation generated by statistical software (seed set such that it is reproducible).
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
Assuming a baseline score of 60 in the control group with a conservative expected improvement of 10 points in the AFEQT score in the SSRI group and a common standard deviation of 20 points, the sample size required for a two-sample t-test of differences between groups is 128 patients. Baseline score and expected improvement in score with pharmacotherapy are based on the original validation study of the AFEQT questionnaire (Spertus et al, 2011). Adding a 20% safety margin to account for loss to follow up and crossover, the total sample size is 154 patients with 77 in each arm.

Baseline characteristics will be described between groups with two sample t tests, chi square tests or Wilcoxon rank sum test.

The primary outcome, AFEQT-based quality of life score, will be assessed between groups using two-sample t-tests according to the intention to treat principle. The change in AFEQT score will be assessed between both groups along with 95% confidence intervals.
Secondary outcomes will be compared descriptively, along with reported p-values and confidence intervals. Non-normally distributed outcomes such as AF burden are expected to be evaluable still with parametric methods due to our sample size of >30 in each arm.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/04/2023
Actual
Date of last participant enrolment
Anticipated
3/02/2025
Actual
Date of last data collection
Anticipated
2/02/2026
Actual
Sample size
Target
154
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22906 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 22907 0
Western Hospital - Footscray - Footscray
Recruitment hospital [3] 22908 0
Sunshine Hospital - St Albans
Recruitment hospital [4] 22909 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 38214 0
3050 - Parkville
Recruitment postcode(s) [2] 38215 0
3011 - Footscray
Recruitment postcode(s) [3] 38216 0
3021 - St Albans
Recruitment postcode(s) [4] 38217 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 311987 0
Hospital
Name [1] 311987 0
Melbourne Health
Country [1] 311987 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country
Australia
Secondary sponsor category [1] 315067 0
None
Name [1] 315067 0
Address [1] 315067 0
Country [1] 315067 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 311410 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 311410 0
Ethics committee country [1] 311410 0
Australia
Date submitted for ethics approval [1] 311410 0
24/07/2022
Approval date [1] 311410 0
Ethics approval number [1] 311410 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120998 0
Prof Jonathan Kalman
Address 120998 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country 120998 0
Australia
Phone 120998 0
+61 3 9349 5400
Fax 120998 0
Email 120998 0
[email protected]
Contact person for public queries
Name 120999 0
Youlin Koh
Address 120999 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country 120999 0
Australia
Phone 120999 0
+61 3 9342 7000
Fax 120999 0
Email 120999 0
[email protected]
Contact person for scientific queries
Name 121000 0
Youlin Koh
Address 121000 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country 121000 0
Australia
Phone 121000 0
+61 3 9342 7000
Fax 121000 0
Email 121000 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
Individual participant data will not be made publicly available to maintain privacy and confidentiality.


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.