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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03305250




Registration number
NCT03305250
Ethics application status
Date submitted
21/09/2017
Date registered
9/10/2017
Date last updated
9/05/2024

Titles & IDs
Public title
Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease
Scientific title
Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease: the Role of Implantable Loop Recorders
Secondary ID [1] 0 0
FD-ILR-001
Universal Trial Number (UTN)
Trial acronym
RaILRoAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Implantable Loop Recorder

Active Comparator: Interventional Arm - Using an Implantable Loop Recorder fo continuous rhythm monitoring and home follow-up. This will be combined with standard care procedure, which will include annual ECG, 24 hour Holter/5 day ECG monitoring and further investigation dependent on symptom status.

No Intervention: Standard of Care Arm - The standard of care with annual ECG, 24 hour Holter/5 day ECG monitoring and further investigation dependent on symptom status.


Treatment: Devices: Implantable Loop Recorder
An implantable loop recorder (ILR), also known as an insertable cardiac monitor, is a small device (smaller than a AAA battery) that is inserted under the skin on the front of the chest. The ILR is inserted using local anesthetic as an out-patient procedure and lasts approximately 30 minutes. The ILR captures a continuous ECG of your heart activity, which allows doctors to detect any abnormal heart rhythms at any point. If you have the ILR, you will have the device for 3 years, after which it will be removed under local anesthetic during an out-patient procedure, again lasting approximately 30 minutes. The ILR device is completely safe and shouldn't affect your day to day living.
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
First occurrence of atrial fibrillation (AF) requiring anticoagulation
Timepoint [1] 0 0
Total monitoring time period in study - 3 years
Primary outcome [2] 0 0
First occurrence of bradyarrhythmia requiring cardiac pacing
Timepoint [2] 0 0
Total monitoring time period in study - 3 years
Primary outcome [3] 0 0
First occurrence of supraventricular arrhythmia requiring drug treatment or ablation.
Timepoint [3] 0 0
Total monitoring time period in study - 3 years
Primary outcome [4] 0 0
First occurrence of non-sustained ventricular tachyarrhythmia requiring drug treatment, ICD implantation or ablation
Timepoint [4] 0 0
Total monitoring time period in study - 3 years
Secondary outcome [1] 0 0
Frequency of arrhythmia in patients with and without late gadolinium enhancement (LGE)
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Frequency of arrhythmia according to location of myocardial fibrosis (inferolateral vs. non-inferolateral)
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Frequency of arrhythmia in those patients with a QRS duration greater or less than 120ms
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Frequency of arrhythmia in those with an atrial size above or below indexed normal range for age and sex
Timepoint [4] 0 0
3 years

Eligibility
Key inclusion criteria
- Patients with genotypically or enzymatically confirmed FD

- Adults > 18 years of age

- Evidence of cardiac involvement from FD involving either:

- Any ECG abnormality associated with FD

- Low T1 on CMR (below centre-specific normal range according to sex)

- LVH on transthoracic echo (defined as MWT >12mm)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient with an existing cardiac device (PPM, ICD or ILR).

- Known dual pathology:

- Known coronary artery disease (positive non-invasive imaging, confirmed myocardial
infarction, percutaneous or surgical revascularisation). Patients >40 years old with
symptoms that could be from coronary artery disease will have this excluded

- Known cardiomyopathy disease causing mutation (e.g. SCN5, MYBPC3)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2027
Actual
Sample size
Target
Accrual to date
Final
169
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
University of Sydney - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
West Midlands
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Cambridge
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Cardiff
Country [4] 0 0
United Kingdom
State/province [4] 0 0
London
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Manchester
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Other
Name
University Hospital Birmingham NHS Foundation Trust
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Free Hospital NHS Foundation Trust
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Northern Care Alliance NHS Foundation Trust
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Sydney
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Cambridge University Hospitals NHS Foundation Trust
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Cardiff and Vale University Health Board
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Sheffield Teaching Hospitals NHS Foundation Trust
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Fabry disease (FD) is a genetic disorder that leads to progressive accumulation of fat or
'sphingolipid' within the tissues, including the heart muscle and conductive tissue.
Improvements in the detection of FD, together with more organised clinical services for rare
diseases, has led to a rapid growth in the disease prevalence. Earlier and more frequent
diagnosis of asymptomatic individuals before development of the disease itself has focused
attention on early detection of organ involvement and closer monitoring of disease
progression. Moreover, the introduction of enzyme replacement therapy within the last two
decades has changed the natural history of FD as follows: a) increased life expectancy; b)
improved morbidity; c) modification of the main cause of morbidity and mortality from renal
(kidney) to cardiovascular (heart) events, including heart failure, abnormal heart rhythms,
stroke and sudden death. Although symptoms such as palpitations and blackouts are extremely
common, information on the frequency of proven abnormal heart rhythms is limited. In
addition, the rate and appropriateness of implantation of life-saving devices is very
variable, including pacemakers to boost the heart when too slow and cardio-defibrillators
that stop the heart when too fast. The main markers of risk in similar diseases such as
hypertrophic cardiomyopathy cannot be used in FD. While patients are routinely followed up in
clinic with heart tracings and echocardiography (ultrasound of the heart), a recent small
study has emphasised that these tests under-estimate the burden of abnormal heart rhythms in
patients with advanced FD. The use of continuous heart monitoring with an implantable loop
recorder (ILR) has led to a significant change in treatment in 13 out of 15 of FD patients.
The investigators believe that more frequent use of ILRs will identify a greater need for
change in therapy in many more patients than currently treated, with the aim of reducing
morbidity and mortality in this patient cohort. In addition this will provide valuable data
to inform an estimate of future risk for these patients.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03305250
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard Steeds, MD
Address 0 0
University Hospital Birmingham NHS Foundation Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03305250