Effect of Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Sacubitril / Valsartan.
- Who it may be relevant to
- Registry conditions: Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM). Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Spain
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Effect of Pharmacological Treatment with Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction (SAVA-TTR)
Overview
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.
Detailed description
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.
Interventions
- Drug Sacubitril / Valsartan
Dose titration of Sacubitril/Valsartán to the maximum tolerated dose (maximum 97/103 mg)
Primary outcome measures
- Change in left ventricular systolic function (%) assessed by echocardiogram. [Time frame: 12 months]
Secondary outcome measures (9)
- Change in left ventricular systolic function assessed by global longitudinal strain (GLS) [Time frame: 12 months]
- Change in E/e' ratio measured by echocardiogram. [Time frame: 12 months]
- Change in functional capacity assessed by 6-minute walk test [Time frame: 12 months]
- Change in quality of life according to the Kansas City Cardiomyopathy Questionnaire [Time frame: 12 months]
- Change in N-terminal pro-B-type natriuretic peptide (NTproBNP) biomarker level. [Time frame: 12 months]
- Proportion of patients experiencing cardiovascular hospitalizations. [Time frame: 12 months]
- Proportion of patients experiencing adverse events [Time frame: 12 months]
- Proportion of patients discontinuing treatment [Time frame: 12 months]
- Proportion of patients experiencing all-cause mortality. [Time frame: 12 months]
Eligibility criteria
Inclusion criteria
- 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).
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
Spain · 1 center
- Hospital Universitario Puerta de Hierro — Majadahonda
Identifiers
NCT: NCT06712030 · 2024-515661-34-00 · 2024-515661-34-00