Cardiac Involvement in Adult Patients With Fabry Disease; Relation to Enzyme Replacement Therapy

Fabry Disease Clinical Trial

Official title: Cardiac Involvement in Adult Patients With Fabry Disease; Relation to Enzyme Replacement Therapy - A Nationwide Danish Clinical Cohort Study

Status Completed

Clinical 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.

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Fabry Disease

• NCT number: NCT02908724
• Study type: Observational
• Source: Rigshospitalet, Denmark
• Status: Completed
• Start date: November 2014
• Completion date: February 9, 2016