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NCT Number: NCT03305250

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Fabry Disease Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Cardiovascular Diseases Central Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Sphingolipidoses Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Sydney, Sydney, Australia

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About this study

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:

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

  • 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)

Treatment and study plan

Implantable Loop Recorder

Device

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.

Primary outcomes

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

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

    This will include all descriptions of AF, which can be defined as:

    • paroxysmal - self-terminating episodes lasting between 48 hours to 7 days
    • persistent - intermittent episodes lasting between 7 days to 1 year
    • permanent - episodes lasting longer than 1 year

  2. First occurrence of bradyarrhythmia requiring cardiac pacing

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

    This would include:

    • Symptomatic significant AV block.
    • Mobitz type 2 AV block or complete heart block irrespective of symptoms.

  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

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

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

Secondary outcomes

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

    Time frame: 3 years

    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.

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

    Time frame: 3 years

    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.

  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

Sponsors and collaborators

Lead sponsor

University Hospital Birmingham NHS Foundation Trust

Other

Collaborators

  • Cambridge University Hospitals NHS Foundation Trust
  • Cardiff and Vale University Health Board
  • Northern Care Alliance NHS Foundation Trust
  • Royal Free Hospital NHS Foundation Trust
  • Sheffield Teaching Hospitals NHS Foundation Trust
  • University of Sydney

Registry information

Official study title

Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease: the Role of Implantable Loop Recorders

Acronym: RaILRoAD

Important dates

Study start
2019
Primary completion
2026
Study completion
2027
First posted
Oct 9, 2017
Registry last updated
May 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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