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Active, not recruitingNCT03305250RaILRoADUpdated May 14, 2025

Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease

An interventional study of Implantable Loop Recorder in Fabry Disease, sponsored by University Hospital Birmingham NHS Foundation Trust. Active, not recruiting at 7 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-14.

Sponsored by University Hospital Birmingham NHS Foundation Trust · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
169
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

This is a 3-year open-label multicentre randomised controlled trial assessing arrhythmia burden in patients with Fabry cardiac disease. This is an observational study, but with implantable loop recorder (ILR) insertion at recruitment and removal at end of trial for the intervention arm.

Null hypothesis: There will be no difference in the identification of arrhythmia between patients following standard care compared to patients following standard care but with the addition of ILR monitoring.

Beyond the proposed hypothesis, data collected will be used to inform whether ILR in FD will:

  1. Reveal a high burden of unrecognised arrhythmia
  2. Lead to frequent treatment modification (anti-coagulation, pacemaker and ICD implantation, ablation)
  3. Enable the development of FD specific risk prediction algorithms
  4. Identify predictive power of new (Troponin, BNP, lysoGB3, T1 and T2 mapping) and traditional biomarkers
02

Conditions studied

03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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)

Exclusion criteria

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)
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
169 participants (actual)

Study arms

  • 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.

    Device: Implantable Loop Recorder

  • 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.

Interventions

  • DeviceImplantable 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.

05

What researchers measure

Primary outcomes

  1. First occurrence of atrial fibrillation (AF) requiring anticoagulation

    This will include all descriptions of AF, which can be defined as: 1. paroxysmal - self-terminating episodes lasting between 48 hours to 7 days 2. persistent - intermittent episodes lasting between 7 days to 1 year 3. permanent - episodes lasting longer than 1 year

    Time frame: Total monitoring time period in study - 3 years

  2. First occurrence of bradyarrhythmia requiring cardiac pacing

    This would include: 1. Symptomatic significant AV block. 2. Mobitz type 2 AV block or complete heart block irrespective of symptoms.

    Time frame: Total monitoring time period in study - 3 years

  3. First occurrence of supraventricular arrhythmia requiring drug treatment or ablation.

    Time frame: Total monitoring time period in study - 3 years

  4. First occurrence of non-sustained ventricular tachyarrhythmia requiring drug treatment, ICD implantation or ablation

    This is classified as three or more ventricular beats at a rate \>120bpm, for a duration of less than 30 seconds.

    Time frame: Total monitoring time period in study - 3 years

Secondary outcomes

  1. Frequency of arrhythmia in patients with and without late gadolinium enhancement (LGE)

    The study will aim at quantifying the extent of LGE deposited with myocardial tissue on cardiac MRI scanning. This will subsequently be correlated with the burden of arrhythmia detected to assess for potential risk factors.

    Time frame: 3 years

  2. Frequency of arrhythmia according to location of myocardial fibrosis (inferolateral vs. non-inferolateral)

    The study will aim to correlate the location of myocardial fibrosis with the presence or absence of cardiac arrhythmia to define location of fibrosis as a potential risk factor for arrhythmia.

    Time frame: 3 years

  3. Frequency of arrhythmia in those patients with a QRS duration greater or less than 120ms

    Time frame: 3 years

  4. Frequency of arrhythmia in those with an atrial size above or below indexed normal range for age and sex

    Time frame: 3 years

06

Study locations

7 sites
  • University of Sydney
    Sydney, Australia
  • University Hospitals Birmingham NHS Foundation Trust
    Birmingham, West Midlands B15 2TH, United Kingdom
  • Cambridge University Hospitals NHS Foundation Trust
    Cambridge, CB2 0QQ, United Kingdom
  • Cardiff and Vale University Health Board
    Cardiff, United Kingdom
  • Royal Free NHS Foundation Trust
    London, NW3 2QG, United Kingdom
  • Salford Royal NHS Foundation Trust
    Manchester, M6 8HD, United Kingdom
  • Sheffield Teaching Hospitals NHS Foundation Trust
    Sheffield, United Kingdom
07

References and documents

Publications

  • Vijapurapu R, Kozor R, Hughes DA, Woolfson P, Jovanovic A, Deegan P, Rusk R, Figtree GA, Tchan M, Whalley D, Kotecha D, Leyva F, Moon J, Geberhiwot T, Steeds RP. A randomised controlled trial evaluating arrhythmia burden, risk of sudden cardiac death and stroke in patients with Fabry disease: the role of implantable loop recorders (RaILRoAD) compared with current standard practice. Trials. 2019 May 31;20(1):314. doi: 10.1186/s13063-019-3425-1. PubMed 31151481 ↗

Individual participant data

Plan to share: No — There is no plan to make individual participant data available to other researchers. Data analysis conducted using anonymised patient data will be shared through publications.

08

Registry details

Key details

Study ID
NCT03305250
Lead sponsor
University Hospital Birmingham NHS Foundation Trust
Collaborators
Royal Free Hospital NHS Foundation Trust, Northern Care Alliance NHS Foundation Trust, University of Sydney, Cambridge University Hospitals NHS Foundation Trust, Cardiff and Vale University Health Board, Sheffield Teaching Hospitals NHS Foundation Trust
Responsible party
Dr Richard Steeds (Consultant in Cardiology, University Hospital Birmingham NHS Foundation Trust) — Principal investigator
First posted
Oct 9, 2017
Start date
Sep 18, 2019
Primary completion
Jul 2026 (estimated)
Completion
Jul 2027 (estimated)
Last update
May 14, 2025

Study contacts

Richard Steeds, MD
principal investigator · University Hospital Birmingham NHS Foundation Trust

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.

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