Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000062224
Ethics application status
Approved
Date submitted
3/01/2018
Date registered
17/01/2018
Date last updated
3/04/2023
Date data sharing statement initially provided
8/01/2019
Date results information initially provided
3/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical impact and treatment outcomes of irregular heart rhythm on human feelings, emotions and intellect
Scientific title
Randomised evaluation of the impact of catheter ablation on psychological distress , neurocognitive function, and arrhythmia outcomes in atrial fibrillation
Secondary ID [1] 293705 0
none
Universal Trial Number (UTN)
U1111-1207-1180
Trial acronym
REMEDIAL study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 306052 0
Psychological distress 306053 0
Neurocognitive function 306054 0
Condition category
Condition code
Mental Health 305191 305191 0 0
Anxiety
Mental Health 305273 305273 0 0
Depression
Mental Health 305274 305274 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Catheter ablation for atrial fibrillation: Patients who are randomly allocated to undergo catheter ablation will undergo this procedure electively in the electrophysiology lab and will be performed by a cardiac electrophysiologist in a public hospital under general anaesthesia. Patients in the interventional arm will also continue to receive standard care in the form of medications including anti-arrhythmic medications, rate controllers and drugs for systemic anticoagulation as deemed appropriate by the treating cardiac electrophysiologist for the duration of the study.
Intervention code [1] 299959 0
Treatment: Surgery
Comparator / control treatment
Medical management of atrial fibrillation: Patients who are randomly allocated to medical management arm will continue to receive standard care in the form of medications only as part of their atrial fibrillation management as deemed appropriate by the treating cardiac electrophysiologist. The commonly used medications include anti-arrhythmic agents, rate-controllers and drugs for systemic anticoagulation. Patients will remain on this standard care for first 12 months of the study.
Participants in the medical arm are then offered an ablation procedure if clinically indicated at the completion of the 12 months trial and the entire cohort is followed up for a further 12 months using the same monitoring protocol as in the initial 12 months.
Control group
Active

Outcomes
Primary outcome [1] 304350 0
Hospital emotional distress as measured using Hospital Anxiety and Depression Scale score
Timepoint [1] 304350 0
Baseline, 3, 6, 9 and 12 months (primary time point) after randomisation
Primary outcome [2] 304352 0
Composite outcome of Cognitive ability as assessed by results of Trail Making tests A and B'
Timepoint [2] 304352 0
Baseline, 3, 6, 9, 12 (primary time point), 18 and 24 months
Primary outcome [3] 334358 0
Arrhythmia free survival at 12 months post catheter ablation.
Patients were followed up either face to face and via telephone at 3, 6, and 12 months post ablation. Intensive rhythm monitoring with either intracardiac monitoring (Implantable loop recorder or permanent pacemaker), or AliveCor twice daily was used to detect arrhythmia recurrences and estimate the AF burden.
Timepoint [3] 334358 0
12 months post catheter ablation.
Secondary outcome [1] 341698 0
Mean University of Toronto AF Severity Scale scores
Timepoint [1] 341698 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [2] 341699 0
Mean Percieved Stress Scale scores
Timepoint [2] 341699 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [3] 341700 0
Type D scale scores
Timepoint [3] 341700 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [4] 341701 0
Mean Beck Depression Inventory Short Form scores
Timepoint [4] 341701 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [5] 341702 0
Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Auditory Verbal Learning Test
Timepoint [5] 341702 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [6] 341705 0
Grooved Peg Board Testing in Dominant Hand
Timepoint [6] 341705 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [7] 341706 0
Symbol Digit Modalities Testing
Timepoint [7] 341706 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [8] 341707 0
CERAD Semantic Fluency Test
Timepoint [8] 341707 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [9] 341708 0
Mini-mental State examination
Timepoint [9] 341708 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [10] 341709 0
Left atrium reservoir function assessments on strain imaging and parameters on echocardiogram
Timepoint [10] 341709 0
Baseline, 6 and 12 months after randoimsation
Secondary outcome [11] 341917 0
Grooved Peg Board Testing Non-dominant Hand
Timepoint [11] 341917 0
Baseline, 3, 6, 9, 12, 18 and 24 months
Secondary outcome [12] 420375 0
Antiarrhythmic medication use
Patients were followed up either face to face and via telephone at 3, 6, and 12 months post ablation.
Timepoint [12] 420375 0
12 months post catheter ablation.
Secondary outcome [13] 420376 0
Median AF burden
Patients were followed up either face to face and via telephone at 3, 6, and 12 months post ablation. Intensive rhythm monitoring with either intracardiac monitoring (Implantable loop recorder or permanent pacemaker), or AliveCor twice daily was used to detect arrhythmia recurrences and estimate the AF burden.
Timepoint [13] 420376 0
12 months post catheter ablation.

Eligibility
Key inclusion criteria
Paroxysmal and persistent atrial fibrillation
Able to give valid consent
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe valvular heart disease
Patients treated for suicidal ideation
Patients being treated for severe depression, anxiety or mood disorders
Pre-existing neurological or clinically evident neurovascular condition
Anticipated difficulty with neurocognitive assessment (deafness, language difficulties)
Contraindication for systemic anticoagulation
Patients who sustain a new cerebrovascular accident during study period
Rheumatic mitral valve disease
Pregnancy

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)
Concealment of allocation will be achieved by using sequentially numbered, opaque sealed envelopes (SNOSE) scheme. The randomisation envelopes will be prepared by an independent statistician.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Categorical variables will be reported as count and percentages, while continuous variables as mean and standard deviations (SD). Continuous outcomes at each endpoint can be analysed using a 2 sample t-test. However, a more comprehensive analysis of continuous outcomes, including additional explanatory variables will be based on a mixed linear model with the participant as the random factor and treatment, site and time as fixed factors. 95% confidence intervals (CI) will be reported. A p-value <0.05 will be considered significant. All analyses will be based on an intention-to-treat model.

Mean treatment differences between groups at baseline and at each follow-up period can be estimated from this model.

Based on our previous results from a non-randomised study looking psychological distress in patients with atrial fibrillation, the average HADS score was noted to be around 11 (in the abnormal range) in this cohort. A useful clinical effect of catheter ablation would be to reduce the mean HADS score to the normal range – the upper limit of which is 7. This corresponds to a mean difference of 4 points. Using this mean difference, and assuming a standard deviation of 5.5, in order for the study to reach a power of 80% with type 1 error of 5%, a minimum of 31 patients will have to be enrolled in each arm.

Sample size calculations were also considered for several other measures, using power of 80% and type I error rate of 5%. In cases where the standard deviations differ between arms, the higher value was used for the sample size calculation.

A sample size of 50 participants in each arm would be sufficient for all scores except for the subscale of SF-36 v2 where-in this sample size would be suitable for detecting an effect of the order of 7 points.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/02/2018
Actual
25/05/2018
Date of last participant enrolment
Anticipated
30/04/2020
Actual
30/04/2020
Date of last data collection
Anticipated
29/04/2022
Actual
29/04/2022
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9676 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 9677 0
The Alfred - Prahran
Recruitment postcode(s) [1] 18442 0
3050 - Parkville
Recruitment postcode(s) [2] 18443 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 298323 0
Self funded/Unfunded
Name [1] 298323 0
Prof Jonathan Kalman
Country [1] 298323 0
Australia
Funding source category [2] 301567 0
Government body
Name [2] 301567 0
NHMRC
Country [2] 301567 0
Australia
Primary sponsor type
Individual
Name
Prof Jonathan Kalman
Address
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country
Australia
Secondary sponsor category [1] 297438 0
Individual
Name [1] 297438 0
Dr Ramanathan Parameswaran
Address [1] 297438 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country [1] 297438 0
Australia
Secondary sponsor category [2] 297510 0
Individual
Name [2] 297510 0
Prof Christina Bryant
Address [2] 297510 0
14-20 Blackwood Street,
North Melbourne.
VIC 3051
Country [2] 297510 0
Australia
Secondary sponsor category [3] 297511 0
Individual
Name [3] 297511 0
Prof Bernard Yan
Address [3] 297511 0
Department of Neurology and Stroke
Royal Melbourne Hospital - City Campus
Level 3, 300 Grattan Street,
Parkville. VIC 3050
Country [3] 297511 0
Australia
Secondary sponsor category [4] 305434 0
Individual
Name [4] 305434 0
Dr Ahmed Al-Kaisey
Address [4] 305434 0
Royal Melbourne Hospital,
Department of Cardiology,
Level 2, 300 Grattan Street, Parkville. VIC 3050
Country [4] 305434 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299316 0
Melbourne Health
Ethics committee address [1] 299316 0
Office of Research
Royal Melbourne Hospital (City Campus)
Level 2, South West
300 Grattan Street
Parkville Victoria 3050
Ethics committee country [1] 299316 0
Australia
Date submitted for ethics approval [1] 299316 0
24/10/2017
Approval date [1] 299316 0
15/01/2018
Ethics approval number [1] 299316 0
HREC/17/MH/347

Summary
Brief summary
The REMEDIAL study aims to better understand the effect of irregular heart rhythm (atrial fibrillation) on human feelings, emotions, clarity of thinking and intellect that impact one's level of functioning and how further management of this condition influences the human mind-heart relationship. Specifically, we intend to study whether management with catheter ablation (a medical procedure for atrial fibrillation) compared with medical therapy (continued treatment with medicines) improves one's level of functioning in these important areas that impact the quality of life.

We hypothesise that this common heart rhythm irregularity causes significant psychological distress and impacts one's intellect and quality of life. We also hypothesise that successful management of atrial fibrillation with catheter ablation will result in a significantly greater improvement in markers of psychological distress and neurocognitive function compared to ongoing medical management.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80030 0
Prof Jonathan Kalman
Address 80030 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country 80030 0
Australia
Phone 80030 0
+61 3 9349 5400
Fax 80030 0
Email 80030 0
[email protected]
Contact person for public queries
Name 80031 0
Dr Ramanathan Parameswaran
Address 80031 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country 80031 0
Australia
Phone 80031 0
+61 3 9342 7000
Fax 80031 0
Email 80031 0
[email protected]
Contact person for scientific queries
Name 80032 0
Dr Ramanathan Parameswaran
Address 80032 0
Department of Cardiology,
Royal Melbourne Hospital - City Campus
Level 2, 300 Grattan Street,
Parkville. VIC 3050
Country 80032 0
Australia
Phone 80032 0
+61 3 9342 7000
Fax 80032 0
Email 80032 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
SourceTitleYear of PublicationDOI
EmbaseAtrial Fibrillation Catheter Ablation vs Medical Therapy and Psychological Distress: A Randomized Clinical Trial.2023https://dx.doi.org/10.1001/jama.2023.14685
EmbaseImpact of Catheter Ablation on Cognitive Function in Atrial Fibrillation: A Randomized Control Trial.2023https://dx.doi.org/10.1016/j.jacep.2023.02.020
N.B. These documents automatically identified may not have been verified by the study sponsor.