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

May 11, 2025 updated by: Dr Richard Steeds, University Hospital Birmingham NHS Foundation Trust

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
169

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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:

  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
Total monitoring time period in study - 3 years
First occurrence of bradyarrhythmia requiring cardiac pacing
Time Frame: Total monitoring time period in study - 3 years

This would include:

  1. Symptomatic significant AV block.
  2. Mobitz type 2 AV block or complete heart block irrespective of symptoms.
Total monitoring time period in study - 3 years
First occurrence of supraventricular arrhythmia requiring drug treatment or ablation.
Time Frame: Total monitoring time period in study - 3 years
Total monitoring time period in study - 3 years
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.
Total monitoring time period in study - 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
3 years
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 years
Frequency of arrhythmia in those patients with a QRS duration greater or less than 120ms
Time Frame: 3 years
3 years
Frequency of arrhythmia in those with an atrial size above or below indexed normal range for age and sex
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Birmingham NHS Foundation Trust

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Northern Care Alliance NHS Foundation Trust
Cambridge University Hospitals NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
Royal Free Hospital NHS Foundation Trust
University of Sydney
Cardiff and Vale University Health Board

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Richard Steeds, MD, University Hospital Birmingham NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 18, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 9, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 14, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FD-ILR-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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