protocolSection identificationModule nctId: NCT06303466, orgStudyIdInfo id: R-23053109, briefTitle: Real World Evidence Study of Danish Fabry Patients, acronym: RWE-FABRY, statusModule overallStatus: ACTIVE_NOT_RECRUITING, startDateStruct date: 2023-08-01, primaryCompletionDateStruct date: 2024-08-01, completionDateStruct date: 2024-12-31, studyFirstPostDateStruct date: 2024-03-12, lastUpdatePostDateStruct date: 2024-03-12, sponsorCollaboratorsModule leadSponsor name: Caroline Michaela Kistorp, class: OTHER, collaborators name: Amicus Therapeutics, collaborators name: Rigshospitalet, Denmark, descriptionModule briefSummary: Fabry is a rare X-linked metabolic lysosomal disorder caused by deficiency in the enzyme α-galactosidase A (alpha-Gal A) by mutations in the GLA gene, encoding the alpha-Gal A enzyme, which catalyses glycosphingolipids, namely globotriaosylceramide (Gb3). Reduced or absent alpha-Gal A activity leads to accumulation of Gb3 in various organs as well as cellular dysfunction and inflammation causing phsyical symptoms and eventual organ failure. Treatment has been available since 2001 for Fabry patients - first enzyme replacement therapy and since 2016, an oral chaperone therapy, Migalastat. Although the initial trials of Migalastat had some both short and extended outcome treatment comparisons, the overall evidence of clinical efficacy is based on too small numbers considering the heterogeneity of the Fabry patient population as well as the very slow progression of the disease. Though the body of real-world evidence is growing, there is a need for more publications of real-world long-term data on clinical outcomes with a focus on treatment with Migalastat.Research Question:Is the incidence and prevalence of Fabry associated clinical events (FACEs) (cardiac, renal, and cerebrovascular) associated with sex, genotype, phenotype at time of diagnosis, biomarkers, and Fabry specific therapy?Objectives:* To investigate time to first Fabry associated clinical events (FACE) (cardiac, renal, and cerebrovascular) with particular focus on Migalastat clinical outcomes and treatment outcomes preceding Migalastat therapy.* To investigate the incidence and prevalence of FACEs with respect to Fabry specific treatment, Migalastat, ERT or no treatment.* To describe FACEs in accordance with different geno- and phenotypic groups.* To investigate the incidence and time to a first fatal or non-fatal cardiac, renal, and cerebrovascular clinical event, separated by each category.Primary outcomes - Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.Secondary outcomes* To investigate the incidence and prevalence of FACEs with respect to Fabry specific treatment, Migalastat, ERT or no treatment.* To describe FACEs in accordance with different geno- and phenotypic groups To investigate the incidence and time to a first fatal or non-fatal cardiac, renal and cerebrovascular clinical event, separated by each category.Exploratory outcomes- To describe disease progression with focus on organ involvement.The study design is a retrospective clinical and paraclinical follow-up of the Danish National Fabry cohort in the period 01.01.2001-31.12.2022. Patient followed a structured yearly monitoring program as part of routine clincal care., conditionsModule conditions: Fabry Disease, designModule studyType: OBSERVATIONAL, designInfo observationalModel: COHORT, timePerspective: RETROSPECTIVE, enrollmentInfo count: 115, type: ESTIMATED, armsInterventionsModule, outcomesModule primaryOutcomes measure: Time to first individual FACE since confirmed diagnosis (Composite endpoint), primaryOutcomes measure: Time to first FACE after initiation of Migalastat treatment (Composite endpoint), secondaryOutcomes measure: Time to first individual FACE since confirmed diagnosis (cardiac), secondaryOutcomes measure: Time to first individual FACE after initiation of Migalastat treatment (cardiac), secondaryOutcomes measure: Time to first individual FACE since confirmed diagnosis (renal), secondaryOutcomes measure: Time to first individual FACE after initiation of Migalastat treatment (renal), secondaryOutcomes measure: Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular), secondaryOutcomes measure: Time to first individual FACE since confirmed diagnosis (cerebrovascular), secondaryOutcomes measure: Prevalence of FACE since confirmed diagnosis, secondaryOutcomes measure: Prevalence of FACE after initiation of Fabry-specific treatment, secondaryOutcomes measure: Incidence of FACE since confirmed diagnosis, secondaryOutcomes measure: Incidence of FACE after initiation of Fabry-specific treatment, secondaryOutcomes measure: Incidence of cardiac events since confirmed diagnosis, secondaryOutcomes measure: Incidence of renal events since confirmed diagnosis, secondaryOutcomes measure: Incidence of cerebrovascular events since confirmed diagnosis, secondaryOutcomes measure: Incidence of cardiac events after initiation of Fabry-specific treatment, secondaryOutcomes measure: Incidence of renal events after initiation of Fabry-specific treatment, secondaryOutcomes measure: Incidence of cerebrovascular events after initiation of Fabry-specific treatment, secondaryOutcomes measure: Annualized rate of change in eGFR by CKDEPI-formula since initiation of treatment, secondaryOutcomes measure: Annualized rate of change in eGFR by CKDEPI-formula after initiation of Fabry-specific treatment, secondaryOutcomes measure: Rapid renal progression of disease since confirmed diagnosis, secondaryOutcomes measure: Rapid renal progression of disease after initiation of Fabry-specific treatment, secondaryOutcomes measure: Incidence of albuminuria since confirmed diagnosis, secondaryOutcomes measure: Incidence of albuminuria after initiation of Fabry-specific treatment, secondaryOutcomes measure: Prevalence of albuminuria since confirmed diagnosis, secondaryOutcomes measure: Prevalence of albuminuria after initiation of Fabry-specific treatment, otherOutcomes measure: Organ-specific decline, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Rigshospitalet, city: Copenhagen, zip: 2100, country: Denmark, geoPoint lat: 55.67594, lon: 12.56553, documentSection largeDocumentModule largeDocs typeAbbrev: Prot, hasProtocol: True, hasSap: False, hasIcf: False, label: Study Protocol, date: 2023-06-30, uploadDate: 2024-02-21T07:57, filename: Prot_000.pdf, size: 1310571, largeDocs typeAbbrev: SAP, hasProtocol: False, hasSap: True, hasIcf: False, label: Statistical Analysis Plan, date: 2023-12-13, uploadDate: 2024-01-12T12:10, filename: SAP_001.pdf, size: 519985, hasResults: False