A Phase 3 interventional study of Sacubitril / Valsartan in Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM), sponsored by Puerta de Hierro University Hospital. Not yet recruiting at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-02.
Sponsored by Puerta de Hierro University Hospital · Phase 3, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Sacubitril/valsartan up to maximum tolerated dose
Drug: Sacubitril / Valsartan
No initiation of Sacubitril/valsartan
Dose titration of Sacubitril/Valsartán to the maximum tolerated dose (maximum 97/103 mg)
Change in left ventricular systolic function (%) assessed by echocardiogram.
Measured by biplane method in percentage
Time frame: 12 months
Change in left ventricular systolic function assessed by global longitudinal strain (GLS)
Measure of longitudinal shortening as a percentage
Time frame: 12 months
Change in E/e' ratio measured by echocardiogram.
Ratio between E wave (peak velocity of early diastolic blood flow across the mitral valve, measured using transmitral Doppler) and E' (E prime): velocity of early diastolic mitral annular motion, measured using tissue Doppler imaging.
Time frame: 12 months
Change in functional capacity assessed by 6-minute walk test
Distance covered over a time of 6 minutes in a flat surface in meters.
Time frame: 12 months
Change in quality of life according to the Kansas City Cardiomyopathy Questionnaire
0 to 100 scale, where 0 is the worst possible health status and 100 best possible health status.
Time frame: 12 months
Change in N-terminal pro-B-type natriuretic peptide (NTproBNP) biomarker level.
Measure in blood. Unit pg/ml.
Time frame: 12 months
Proportion of patients experiencing cardiovascular hospitalizations.
Time frame: 12 months
Proportion of patients experiencing adverse events
Including serious adverse event, grade 3-4 adverse event, adverse reaction, adverse event of special interest.
Time frame: 12 months
Proportion of patients discontinuing treatment
Time frame: 12 months
Proportion of patients experiencing all-cause mortality.
Time frame: 12 months
Plan to share: Yes — Under agreement, individual or aggregated patient data could be shared with other scientific groups for scientific projects. Data can be shared only for scientific purposes and in full compliance with Personal Data Protection requirements in the EU.
Supporting information: Study protocol, Sap, Icf
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Puerta de Hierro University Hospital