Effect of Pharmacological Treatment with Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction (SAVA-TTR)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Change in left ventricular systolic function (%) assessed by echocardiogram.
研究概览
简要总结
Prospective, randomized, multicenter, open-label clinical trial to evaluate the safety and efficacy of Sacubitril/Valsartan (Sac/Vals) compared to no initiation of the drug in patients with transthyretin cardiac amyloidosis (ATTR) and heart failure with reduced ejection fraction (LVEF ≤40%). The primary objective is to determine the impact of Sac/Vals treatment on systolic function by assessing the change in LVEF on echocardiogram at 12-month follow-up.
详细描述
Transthyretin cardiac amyloidosis (ATTR) has emerged as a prevalent and underdiagnosed cause of heart failure (HF), affecting patients both with preserved left ventricular ejection fraction (LVEF) and with systolic dysfunction. It remains unclear whether this population benefits from standard treatments for HF with reduced LVEF or whether treatment with renin-angiotensin system inhibitors and neprilysin might even be harmful in ATTR.
The investigators plan to conduct a prospective, randomized, multicenter, open-label clinical trial to evaluate the safety and efficacy of Sacubitril/Valsartan (Sac/Vals), as recommended in current HF guidelines, versus no treatment in patients with ATTR and heart failure with reduced ejection fraction (HFrEF), including those with LVEF ≤40%.
Approximately 114 patients from four Spanish centers will be randomized 1:1 to receive Sac/Vals treatment (up to the maximum tolerated dose) or to not initiate the drug, with stratification by center and tafamidis treatment. It has been included a run-in period with a low dose of Sac/Vals to assess tolerance prior to randomization. Patients will have scheduled follow-up visits at 3, 6, and 12 months, during which clinical, functional, analytical, electrocardiographic, and echocardiographic variables will be evaluated.
The primary objective is to determine the impact of Sac/Vals treatment on systolic function in patients with ATTR and HFrEF by assessing the change in LVEF on echocardiogram at 12 months. Improvement in LVEF will be defined as an increase of ≥5% from the baseline echocardiogram to the 12-month follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The analysis of the echocardiogram will be performed by evaluators blinded to the treatment and the timing of the imaging.
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
- •Patients ≥ 18 years of age of both sexes.
- •Patients diagnosed with ATTR cardiac amyloidosis as indicated in guidelines, both in its hereditary form (ATTRv) or wild-type form (ATTRwt).
- •Patients initially evaluated or under follow-up in Cardiomyopathy/Heart Failure/Amyloidosis Units at participating centers.
- •Heart failure and reduced ejection fraction: LVEF ≤40%, in functional class I, II, or III according to the New York Heart Association (NYHA).
排除标准
- •NYHA Functional Class IV.
- •Stage 4 and 5 chronic kidney disease (creatinine clearance by CKD-EPI <30 mL/min/1.73m²).
- •Hyperkalemia (blood potassium levels > 5.4 mmol/L).
- •Hypotension defined as systolic blood pressure (SBP) <100 mmHg on two consecutive measurements.
- •Treatment with ACE inhibitors, ARBs, or sacubitril/valsartan at the time of enrollment.
- •History of angioedema or hypersensitivity to ACE inhibitors or ARBs.
- •Treatment with TTR gene silencers or diflunisal.
- •Participation in another clinical trial.
- •Pregnancy, breastfeeding, or fertile women unwilling to use adequate contraception throughout the study duration.
- •Any condition that, in the investigator's opinion, compromises participation in the study.
研究组 & 干预措施
Sacubitril/Valsartan
Sacubitril/valsartan up to maximum tolerated dose
干预措施: Sacubitril / Valsartan (Drug)
结局指标
主要结局
Change in left ventricular systolic function (%) assessed by echocardiogram.
时间窗: 12 months
Measured by biplane method in percentage
次要结局
- Change in left ventricular systolic function assessed by global longitudinal strain (GLS)(12 months)
- Change in E/e' ratio measured by echocardiogram.(12 months)
- Change in functional capacity assessed by 6-minute walk test(12 months)
- Change in quality of life according to the Kansas City Cardiomyopathy Questionnaire(12 months)
- Change in N-terminal pro-B-type natriuretic peptide (NTproBNP) biomarker level.(12 months)
- Proportion of patients experiencing cardiovascular hospitalizations.(12 months)
- Proportion of patients experiencing adverse events(12 months)
- Proportion of patients discontinuing treatment(12 months)
- Proportion of patients experiencing all-cause mortality.(12 months)
研究者
Esther Gonzalez López
Principal Investigator
Puerta de Hierro University Hospital