Effect of Genetic Polymorphisms on the Clinical Response to Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors in Prevention of Cardiac Remodeling and Fibrosis in Heart Failure Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 282
- 试验地点
- 1
- 主要终点
- Median / Mean of Left Ventricular Ejection Fraction (LVEF) among studied genetic polymorphisms
研究概览
简要总结
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown further reductions in heart failure hospitalization, cardiovascular events, and mortality, especially for heart failure patients.
The SGLT2 gene, also known as SLC5A2 (solute carrier family 5 member 2), is located on chromosome 16 and is responsible for encoding SGLT2.
Several SLC5A2 mutations alter SGLT2 expression, membrane location, or transporter function.
Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors.
详细描述
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), which were first investigated and licensed for the treatment of diabetes, are now emerging as a promising class of drugs for the treatment of heart failure (HF), even in people without diabetes.
Significant reductions in worsening heart failure or cardiovascular death were shown under treatment with dapagliflozin and empagliflozin in the trials of patients with heart failure.
Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors.
The most recent SLC5A2 Single Nucleotide Polymorphisms (SNPs) that reduce the risk of heart failure included two intronic SLC5A2 SNPs, s9934336, and rs3116150, both associated with the expression levels of the transporter.
This study aims to detect the association between SLC5A2 single nucleotide polymorphisms and variability in response to SGLT2 Inhibitors as well as the association between cardiac biomarkers and non-coding RNA in patients with Heart Failure.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Heart failure patients NYHA class II to III.
- •Heart failure patients with reduced left ventricular ejection fraction (LVEF) < 45% or with preserved left ventricular ejection fraction (LVEF) > 45%
- •Patients who will be candidate for add-on treatment with SGLT
- •Patients who will be able to sign informed consent to participate in the study.
排除标准
- •Contraindications to SGLT
- •Significant coronary artery diseases (CAD), coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or valve surgery within 3 months.
- •Pregnant or breastfeeding women.
- •Patients with estimated glomerular filtration rates less than 30 mL/min/1.73 m2, as determined using the CKD-EPI equation.
研究组 & 干预措施
Heart Failure Patients with reduced or preserved Ejection Fraction
Patients with reduced or preserved ejection fraction that have received the Guided Therapy (β-blockers, Diuretics, Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs) or Angiotensin Receptor-Neprilysin Inhibitor (ARNi) and Mineralocorticoid receptor antagonists (MRAs) then Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) (10 mg of dapagliflozin or empagliflozin) will be added at the study entry.
干预措施: SGLT2 inhibitors (Dapagliflozin and Empagliflozin) (Drug)
结局指标
主要结局
Median / Mean of Left Ventricular Ejection Fraction (LVEF) among studied genetic polymorphisms
时间窗: 6 months
Change in median / mean of Left Ventricular Ejection Fraction (LVEF) before and after drug administration
Median / Mean of Left Ventricular End Systolic Volumes among studied genetic polymorphisms
时间窗: 6 months
Change in median / mean of Left Ventricular End Systolic Volume (LVESV)
Median / Mean of Left Ventricular End Diastolic Volumes among studied genetic polymorphisms
时间窗: 6 months
Change in median / mean of Left Ventricular End Diastolic Volume (LVEDV) before and after drug administration
次要结局
- Median / Mean of quality of life measure {Kansas City Cardiomyopathy Questionnaire (KCCQ-12)} among studied genetic polymorphisms(6 months)
研究者
Ahmed Essam
Assistant Lecturer in Clinical Pharmacy Department
October 6 University