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

NCT03305250 | Active Not Recruiting DMC

• 1 other identifier: FD-ILR-001
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 7

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.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (4)

• 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

  Total monitoring time period in study - 3 years

• 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.

  Total monitoring time period in study - 3 years

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

  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.

  Total monitoring time period in study - 3 years

Secondary Outcomes (4)

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

  3 years

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

  3 years

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

  3 years

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

  3 years

Study Arms (2)

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.

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.

Interventions

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.

Interventional Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (7)

University of Sydney

Sydney, Australia

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Cardiff and Vale University Health Board

Cardiff, United Kingdom

Location

Royal Free NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Salford Royal NHS Foundation Trust

Manchester, M6 8HD, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31151481 DERIVED

MeSH Terms

Conditions

Fabry Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Richard Steeds, MD

  University Hospital Birmingham NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Cardiology

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: October 9, 2017
• Study Start: September 18, 2019
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: May 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); AU (1)