Fabry DiseaseRaILRoADNCT03305250
Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease
A study testing Implantable Loop Recorder in people with Fabry Disease, run by University Hospital Birmingham NHS Foundation Trust at 7 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fabry Disease
- What is being tested?
- Implantable Loop Recorder
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 18 Sep 2019to Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United Kingdom6 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, West Midlands, B15 2TH
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
Cardiff and Vale University Health Board
Cardiff
Royal Free NHS Foundation Trust
London, NW3 2QG
Salford Royal NHS Foundation Trust
Manchester, M6 8HD
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield
About this study
Official title: 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.
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:
- 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
- Conditions
- Fabry Disease
- Being tested
- Implantable Loop Recorder
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implantable Loop RecorderDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Interventional Arm | Active comparator | 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. Receives: Device: Implantable Loop Recorder |
| Standard of Care Arm | No intervention | The standard of care with annual ECG, 24 hour Holter/5 day ECG monitoring and further investigation dependent on symptom status. |
What is being measured
The primary outcome is the main question the study is designed to answer.
First occurrence of atrial fibrillation (AF) requiring anticoagulation
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
Measured: Total monitoring time period in study - 3 years
First occurrence of bradyarrhythmia requiring cardiac pacing
This would include:
- Symptomatic significant AV block.
- Mobitz type 2 AV block or complete heart block irrespective of symptoms.
Measured: Total monitoring time period in study - 3 years
First occurrence of supraventricular arrhythmia requiring drug treatment or ablation.
Measured: Total monitoring time period in study - 3 years
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.
Measured: Total monitoring time period in study - 3 years
Secondary outcomes (4)
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.
Measured: 3 years
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.
Measured: 3 years
Frequency of arrhythmia in those patients with a QRS duration greater or less than 120ms
Measured: 3 years
Frequency of arrhythmia in those with an atrial size above or below indexed normal range for age and sex
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2017
- Study start18 Sep 2019
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham NHS Foundation Trust
- Sponsor type
- University, hospital or other
- 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
- Principal investigator, Dr Richard Steeds, University Hospital Birmingham NHS Foundation Trust
- Investigators
- Richard Steeds, MD, Principal investigator, University Hospital Birmingham NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03305250
- Sponsor's protocol ID
- FD-ILR-001
- Acronym
- RaILRoAD
- Status last verified
- Dec 2024
- First submitted
- 21 Sep 2017
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
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
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arrhythmia Burden, Risk of Sudden Cardiac Death and Stroke in Patients With Fabry Disease: the Role of Implantable Loop Recorders
- ClinicalTrials.gov ID
- NCT03305250
- Acronym / sponsor ID
- RaILRoAD / FD-ILR-001
- Conditions
- Fabry Disease
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 169 participants (actual)
- Lead sponsor
- University Hospital Birmingham NHS Foundation TrustUniversity, hospital or other
- 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
- Study start
- 18 Sep 2019 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 9 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interventional Arm | Active comparator | Device: Implantable Loop RecorderUsing 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. |
| Standard of Care Arm | No intervention | –The standard of care with annual ECG, 24 hour Holter/5 day ECG monitoring and further investigation dependent on symptom status. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Implantable Loop RecorderAn 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. | Device | Interventional Arm |
Primary outcome
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
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.
First occurrence of supraventricular arrhythmia requiring drug treatment or ablation.
Time frame: 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.
4 secondary outcomes
Frequency of arrhythmia in patients with and without late gadolinium enhancement (LGE)
Time frame: 3 years
Frequency of arrhythmia according to location of myocardial fibrosis (inferolateral vs. non-inferolateral)
Time frame: 3 years
Frequency of arrhythmia in those patients with a QRS duration greater or less than 120ms
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Derived from this study: PubMed 31151481Vijapurapu 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Steeds, MD principal investigator
University Hospital Birmingham NHS Foundation Trust
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Implantable Loop Recorder in people with Fabry Disease, run by University Hospital Birmingham NHS Foundation Trust at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First occurrence of atrial fibrillation (AF) requiring anticoagulation (time frame: Total monitoring time period in study - 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03305250, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.