Fabry DiseaseNCT02908724
Cardiac Involvement in Adult Patients With Fabry Disease; Relation to Enzyme Replacement Therapy
An observational study of Fabry Disease, run by Ulla Feldt-Rasmussen.
Trial summary
The purpose of this study was to assess the progression of cardiac involvement in adult patients with Fabry Disease (FD), in the unique Danish Fabry cohort and comparing those FD patients receiving primary therapy vs. those that did not. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fabry Disease
- How many people
- 66 participants
- Where
- No sites listed yet
- Study dates
- Nov 2014to 9 Feb 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Sixty-six patients with FD
Who may be able to join
- Genetically verified Fabry disease
- Age at baseline >18 years
- Baseline cardiac examination performed
Who cannot join
- Switch from FD specific treatment (Fabrazyme or Replagal) to no FD specific treatment
About this study
Official title: Cardiac Involvement in Adult Patients With Fabry Disease; Relation to Enzyme Replacement Therapy - A Nationwide Danish Clinical Cohort Study
The purpose of this study was to assess the progression of cardiac involvement in adult patients with Fabry Disease (FD), in the unique Danish Fabry cohort and comparing those FD patients receiving primary therapy vs. those that did not.
The hypothesis is, that we will not be able to see a significant positive difference in cardiac involvement in those FD patient who received FD specific therapy vs. those that did not.
Read the detailed description
Enzyme replacement therapy and concomitant treatment:
FD specific treatment (ERT, enzyme replacement therapy) have been available since 2001 and patients have been treated with either agalsidase alpha (Replagal®) or agalsidase beta (Fabrazyme®) every other week at recommended doses, 0.2 mg/kg and 1.0 mg/kg, respectively.
Concomitant treatment with cardiovascular medication including angiotensin-converting-enzyme-inhibitor, angiotensin-II-receptor-blocker, acetylsalicylic acid, beta-blocker, calcium-channel-blocker, diuretics and statins, was registered for all patients.
Statistical analysis:
Primarily, we compared the progression of cardiac involvement from baseline to follow-up, according to ERT including subgroup analysis according to gender.
Secondarily, subgroup analysis of the ERT group was performed by separating patients with- and without cardiac disease at baseline, indicated by the presence of myocardial hypertrophy on transthoracic echocardiography (septal thickness or LV posterior wall thickness >0.9 cm for females and >1.0 for males), increased cardiac mass (Left ventricular mass index (LVMi) >95 g/m2 for females and >115g/m2 for males) or systolic dysfunction (ejection fraction <55%) in accordance with the guidelines from the American Society of Echocardiography and the European Association of Echocardiography (Lang et al., 2005).
In these analyses ERT patients' baseline was defined as the last available examination prior to ERT start and follow-up as the last available examination during ERT. Inclusion in the non-ERT group required that patient had not received ERT at study end. Intra-group comparisons of progression from baseline to follow-up were made by McNemar test (categorical variables) and Wilcoxon Signed Rank Test (continuous variables).
Thirdly, for comparisons between treatment groups, linear mixed models were applied on all available data from continuous variables regarding Sokolow-Lyon voltage-, Cornell product ECG criteria and LVMi as no violations of the assumptions for linear mixed model testing were found in initial analyses. The modelling allows for individual difference at a general level (tracking) as well as individual differences in the progression over time, controlled for gender, age at baseline, treatment duration and current ERT status.
Comparisons of major organ involvement at baseline, gene mutations and alfa-galactosidase A activity between treatment groups, were performed by Chi-squared and Mann-Whitney U tests, respectively.
Data from categorical variables are presented as frequency (percentage), and continuous variables are presented as median [range] or estimate (±standard error). Data was analysed using SPSS (version 19.0). All tests were two-sided and a p-value <0.05 was considered statistically significant.
- Conditions
- Fabry Disease
- Keywords
- Familial cardiomyopathies, Hypertrophic cardiomyopathy, Left ventricular hypertrophy
- Medical subject headings
- Fabry Disease, Cardiomyopathy, Hypertrophic, Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| ERT receiving patients | Patients that were receiving specific treatment for FD (ERT, enzyme replacement therapy, Fabrazyme or Replagal) during the observational time (n= 47). | |
| non-ERT receiving patients | Patients that were not receiving specific treatment for FD (ERT, enzyme replacement therapy, Fabrazyme or Replagal) during the observational time (n= 19). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left Ventricular Mass Index
Measured by Transthoracic Echocardiography using a Philips IE 33. Two-dimensional parasternal images were used to determine left ventricular chamber dimensions and wall thickness; LV mass was calculated by the American Society of Echocardiography (ASE) equation and indexed to body surface area. Median [range] is evaluated and presented.
Measured: Up to 13 years follow-up
Left Ventricular Hypertrophy - Sokolow-Lyon voltage criteria
12-lead electrocardiography (ECG) was performed using a Schiller Cardiovit AT-2 (Schiller AG, Dietikon, Switzerland). Left ventricular hypertrophy was evaluated by Sokolow-Lyon voltage criteria (S in V1 + R in V5/V6 ≥ 35 mm). Median [range] and frequency (%) of hypertrophy is evaluated and presented.
Measured: Up to 13 years follow-up
Left Ventricular Hypertrophy - Cornell voltage product criteria
12-lead ECG was performed using a Schiller Cardiovit AT-2 (Schiller AG, Dietikon, Switzerland). Left ventricular hypertrophy was evaluated by Cornell product criteria (R in aVL + S in V3 (+6 mm for women) x QRS duration > 2440 mm·ms). Median [range] and frequency (%) of hypertrophy is evaluated and presented.
Measured: Up to 13 years follow-up
Secondary outcomes (2)
Clinical outcome
Cardiac interventions (medication, percutaneous coronary interventions, coronary artery bypass graft, implantation of implantable cardioverter-defibrillators or pacemakers), Cardiac symptoms (Chest pain, palpitations, edema, dyspnea, dizziness, syncope) and all-cause mortality. Frequency (%) is evaluated and presented.
Measured: Up to 13 years follow-up
Arrhythmias
Atrial fibrillation, atrial flutter, supraventricular tachycardia, non-sustained ventricular tachycardia, measured by ECG and Holter-monitoring. Frequency (%) is evaluated and presented.
Measured: Up to 13 years follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2016 (estimated)
- Study startNov 2014
- Primary completionNov 2014
- Study completion9 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ulla Feldt-Rasmussen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ulla Feldt-Rasmussen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Ulla Feldt-Rasmussen, MD,DMSc,Prof, Principal investigator, Department of Medical Endocrinology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02908724
- Sponsor's protocol ID
- FAB-ECG
- Status last verified
- Oct 2018
- First submitted
- 4 Apr 2016
- Last updated
- 16 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Involvement in Adult Patients With Fabry Disease; Relation to Enzyme Replacement Therapy - A Nationwide Danish Clinical Cohort Study
- ClinicalTrials.gov ID
- NCT02908724
- Acronym / sponsor ID
- FAB-ECG
- Conditions
- Fabry Disease
- Keywords
- Familial cardiomyopathies, Hypertrophic cardiomyopathy, Left ventricular hypertrophy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Ulla Feldt-RasmussenUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Nov 2014 (actual)
- Study completion
- 9 Feb 2016 (actual)
- First posted
- 21 Sep 2016 (estimated)
- 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.
The purpose of this study was to assess the progression of cardiac involvement in adult patients with Fabry Disease (FD), in the unique Danish Fabry cohort and comparing those FD patients receiving primary therapy vs. those that did not.
The hypothesis is, that we will not be able to see a significant positive difference in cardiac involvement in those FD patient who received FD specific therapy vs. those that did not.
Detailed description
Enzyme replacement therapy and concomitant treatment:
FD specific treatment (ERT, enzyme replacement therapy) have been available since 2001 and patients have been treated with either agalsidase alpha (Replagal®) or agalsidase beta (Fabrazyme®) every other week at recommended doses, 0.2 mg/kg and 1.0 mg/kg, respectively.
Concomitant treatment with cardiovascular medication including angiotensin-converting-enzyme-inhibitor, angiotensin-II-receptor-blocker, acetylsalicylic acid, beta-blocker, calcium-channel-blocker, diuretics and statins, was registered for all patients.
Statistical analysis:
Primarily, we compared the progression of cardiac involvement from baseline to follow-up, according to ERT including subgroup analysis according to gender.
Secondarily, subgroup analysis of the ERT group was performed by separating patients with- and without cardiac disease at baseline, indicated by the presence of myocardial hypertrophy on transthoracic echocardiography (septal thickness or LV posterior wall thickness >0.9 cm for females and >1.0 for males), increased cardiac mass (Left ventricular mass index (LVMi) >95 g/m2 for females and >115g/m2 for males) or systolic dysfunction (ejection fraction <55%) in accordance with the guidelines from the American Society of Echocardiography and the European Association of Echocardiography (Lang et al., 2005).
In these analyses ERT patients' baseline was defined as the last available examination prior to ERT start and follow-up as the last available examination during ERT. Inclusion in the non-ERT group required that patient had not received ERT at study end. Intra-group comparisons of progression from baseline to follow-up were made by McNemar test (categorical variables) and Wilcoxon Signed Rank Test (continuous variables).
Thirdly, for comparisons between treatment groups, linear mixed models were applied on all available data from continuous variables regarding Sokolow-Lyon voltage-, Cornell product ECG criteria and LVMi as no violations of the assumptions for linear mixed model testing were found in initial analyses. The modelling allows for individual difference at a general level (tracking) as well as individual differences in the progression over time, controlled for gender, age at baseline, treatment duration and current ERT status.
Comparisons of major organ involvement at baseline, gene mutations and alfa-galactosidase A activity between treatment groups, were performed by Chi-squared and Mann-Whitney U tests, respectively.
Data from categorical variables are presented as frequency (percentage), and continuous variables are presented as median [range] or estimate (±standard error). Data was analysed using SPSS (version 19.0). All tests were two-sided and a p-value <0.05 was considered statistically significant.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ERT receiving patients | – | –Patients that were receiving specific treatment for FD (ERT, enzyme replacement therapy, Fabrazyme or Replagal) during the observational time (n= 47). |
| non-ERT receiving patients | – | –Patients that were not receiving specific treatment for FD (ERT, enzyme replacement therapy, Fabrazyme or Replagal) during the observational time (n= 19). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Sixty-six patients with FD
Key inclusion criteria (3 listed)
- Genetically verified Fabry disease
- Age at baseline >18 years
- Baseline cardiac examination performed
Key exclusion criteria (1 listed)
- Switch from FD specific treatment (Fabrazyme or Replagal) to no FD specific treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Left Ventricular Mass Index
Time frame: Up to 13 years follow-up
Measured by Transthoracic Echocardiography using a Philips IE 33. Two-dimensional parasternal images were used to determine left ventricular chamber dimensions and wall thickness; LV mass was calculated by the American Society of Echocardiography (ASE) equation and indexed to body surface area. Median [range] is evaluated and presented.
Left Ventricular Hypertrophy - Sokolow-Lyon voltage criteria
Time frame: Up to 13 years follow-up
12-lead electrocardiography (ECG) was performed using a Schiller Cardiovit AT-2 (Schiller AG, Dietikon, Switzerland). Left ventricular hypertrophy was evaluated by Sokolow-Lyon voltage criteria (S in V1 + R in V5/V6 ≥ 35 mm). Median [range] and frequency (%) of hypertrophy is evaluated and presented.
Left Ventricular Hypertrophy - Cornell voltage product criteria
Time frame: Up to 13 years follow-up
12-lead ECG was performed using a Schiller Cardiovit AT-2 (Schiller AG, Dietikon, Switzerland). Left ventricular hypertrophy was evaluated by Cornell product criteria (R in aVL + S in V3 (+6 mm for women) x QRS duration > 2440 mm·ms). Median [range] and frequency (%) of hypertrophy is evaluated and presented.
2 secondary outcomes
Clinical outcome
Time frame: Up to 13 years follow-up
Arrhythmias
Time frame: Up to 13 years follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Individual participant dataSharing planned: No
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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.
Ulla Feldt-Rasmussen, MD,DMSc,Prof principal investigator
Department of Medical Endocrinology
Questions about this trial
What is this clinical trial studying?
An observational study of Fabry Disease, run by Ulla Feldt-Rasmussen.
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 3 inclusion and 1 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: finished, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Left Ventricular Mass Index (time frame: Up to 13 years follow-up). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2018.