ClinicalTrials.gov record NCT06712030

Effect of Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

Effect of Pharmacological Treatment with Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction (SAVA-TTR)

StatusNot yet recruitingThe study has been registered but has not started enrolling. Sites and contacts may not be listed yet.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 3A later-stage study, usually with more participants, designed to give stronger evidence about how well a treatment works and how safe it is. It often compares the treatment with standard care or a placebo, and results may support an application for approval.
Age18 years old and older
SexAll
LocationSpain
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Prospective, randomized, multicenter phase 3 trial comparing Sacubitril/Valsartan to no initiation in people with transthyretin cardiac amyloidosis (ATTR-CM) and reduced left ventricular ejection fraction (LVEF ≤40%). About 114 participants will be randomized 1:1 after a low-dose run-in to assess tolerance. Scheduled follow-up visits at 3, 6, and 12 months include clinical checks, blood tests, ECG, and echocardiography. The primary outcome is change in LVEF at 12 months.

What it is studying. Whether starting Sacubitril/Valsartan versus not starting it affects heart systolic function and safety in people with ATTR-CM and reduced LVEF, with the main measure being change in left ventricular ejection fraction at 12 months.

What the researchers hope to learn. Determine the effect of Sacubitril/Valsartan on left ventricular systolic function (change in LVEF at 12 months). Secondary goals include measuring changes in global longitudinal strain, E/e' ratio, 6-minute walk distance, quality of life (Kansas City Cardiomyopathy Questionnaire), NT‑proBNP levels, cardiovascular hospitalizations, adverse events, treatment discontinuation, and all-cause mortality.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Sacubitril / Valsartan

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

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.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

After a low‑dose run‑in to assess tolerance, eligible patients are randomized 1:1 to start sacubitril/valsartan (titrated to the maximum tolerated dose, up to 97/103 mg) or to not initiate the drug. Scheduled visits at 3, 6 and 12 months collect clinical information, functional tests, blood tests, electrocardiograms and echocardiograms (including LVEF, global longitudinal strain and E/e'), a 6‑minute walk test, and a quality‑of‑life questionnaire; NT‑proBNP blood levels and hospitalizations/adverse events are also recorded. The active arm involves medication dose titration and safety monitoring; the study follows participants for outcomes and any treatment discontinuation over 12 months.

How the study is structured. Interventional, phase 3, randomized, parallel-group trial. Participants are assigned 1:1 to Sacubitril/Valsartan (dose titrated to maximum tolerated, up to 97/103 mg) or to not initiate Sacubitril/Valsartan. The registry describes the trial as open-label; masking is listed as single. Follow-up visits at 3, 6, and 12 months include clinical assessment, blood tests, ECG, and echocardiography.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM). Does it apply to my diagnosis?
  • The registry says recruitment has not started. When is it expected to open, and can I register interest now?
  • The listed sites are in Spain. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on ATTRv amyloidosis

This trial is also listed on this site under wild-type ATTR amyloidosis.

Clinical trials106 trials listed for ATTRv amyloidosisEvery trial the registry lists for ATTRv amyloidosis, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in ATTRv amyloidosis researchLatest monthly update: September 2026. Includes: Gene-silencing drugs. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
January 2025 (estimated)
Primary completion
April 2027 (estimated)
Study completion
June 2027 (estimated)
Target enrollment
114 participants (estimated)
Last updated on registry
Dec 2, 2024
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Puerta de Hierro University Hospital
Principal investigator
Esther Gonzalez López, Principal Investigator
Puerta de Hierro University Hospital

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
primary objective
The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
echocardiogram
An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
1:1
How many participants go to each group. In a 2:1 ratio, two are assigned to the first group for every one assigned to the second.
maximum tolerated dose
The highest dose found in a dose-escalation study that can be given without too many dose-limiting side effects.
run-in period
A period at the start of a study, before the study treatment begins, used for example to confirm that participants meet the criteria or to record their usual symptoms.
baseline
Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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