Real World Evidence Study of Danish Fabry Patients: a >20- Year Longitudinal Retrospective Analysis of Prospectively Collected Data.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Time to first individual FACE since confirmed diagnosis (Composite endpoint)
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically-verified Fabry disease
- •Age above or equal to 18
排除标准
- 未提供
结局指标
主要结局
Time to first individual FACE since confirmed diagnosis (Composite endpoint)
时间窗: 10 years post baseline
Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time to first FACE after initiation of Migalastat treatment (Composite endpoint)
时间窗: 5 years post baseline
Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
次要结局
- Prevalence of FACE since confirmed diagnosis(20 years post baseline)
- Incidence of renal events after initiation of Fabry-specific treatment(5 years post baseline)
- Time to first individual FACE since confirmed diagnosis (cardiac)(10 years post baseline)
- Time to first individual FACE after initiation of Migalastat treatment (cardiac)(5 years post baseline)
- Incidence of FACE after initiation of Fabry-specific treatment(5 years post baseline)
- Incidence of cerebrovascular events after initiation of Fabry-specific treatment(5 years post baseline)
- Annualized rate of change in eGFR by CKDEPI-formula since initiation of treatment(20 years post baseline)
- Rapid renal progression of disease after initiation of Fabry-specific treatment(5 years post baseline)
- Incidence of albuminuria since confirmed diagnosis(20 years post baseline)
- Incidence of cardiac events after initiation of Fabry-specific treatment(5 years post baseline)
- Time to first individual FACE since confirmed diagnosis (renal)(10 years post baseline)
- Time to first individual FACE after initiation of Migalastat treatment (renal)(5 years post baseline)
- Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular)(5 years post baseline)
- Time to first individual FACE since confirmed diagnosis (cerebrovascular)(10 years post baseline)
- Prevalence of FACE after initiation of Fabry-specific treatment(5 years post baseline)
- Incidence of cardiac events since confirmed diagnosis(20 years post baseline)
- Incidence of renal events since confirmed diagnosis(20 years post baseline)
- Incidence of cerebrovascular events since confirmed diagnosis(20 years post baseline)
- Rapid renal progression of disease since confirmed diagnosis(20 years post baseline)
- Incidence of FACE since confirmed diagnosis(20 years post baseline)
- Annualized rate of change in eGFR by CKDEPI-formula after initiation of Fabry-specific treatment(5 years post baseline)
- Incidence of albuminuria after initiation of Fabry-specific treatment(5 years post baseline)
- Prevalence of albuminuria since confirmed diagnosis(20 years post baseline)
- Prevalence of albuminuria after initiation of Fabry-specific treatment(5 years post baseline)
研究者
Caroline Michaela Kistorp
Professor
Rigshospitalet, Denmark