Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)Phase 3SAVA-TTRNCT06712030
Effect of Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction
A Phase 3 study testing Sacubitril / Valsartan in people with Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM), run by Puerta de Hierro University Hospital at 1 site in Spain.
Trial summary
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%). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)
- What is being tested?
- Sacubitril / Valsartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2025to Jun 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, 28222
Esther Gonzalez Lopez, MD, PhD, +34 91 1916000, egonzalezlopez@salud.madrid.org
Noemí Ramos López, nramosl@cnic.es
About this study
Official title: Effect of Pharmacological Treatment with Angiotensin Receptor/Neprilysin Inhibitors on Transthyretin Cardiac Amyloidosis and Heart Failure with Reduced Ejection Fraction (SAVA-TTR)
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.
Read the 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.
- Being tested
- Sacubitril / Valsartan
- Keywords
- Heart failure, Reduced ejection fraction, Angiotensin receptor/neprilysin inhibitors, Sacubitril valsartan
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril / ValsartanDrug
Dose titration of Sacubitril/Valsartán to the maximum tolerated dose (maximum 97/103 mg)
| Study group | Role | What they receive |
|---|---|---|
| Sacubitril/Valsartan | Experimental | Sacubitril/valsartan up to maximum tolerated dose Receives: Drug: Sacubitril / Valsartan |
| No treatment | No intervention | No initiation of Sacubitril/valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular systolic function (%) assessed by echocardiogram.
Measured by biplane method in percentage
Measured: 12 months
Secondary outcomes (9)
Change in left ventricular systolic function assessed by global longitudinal strain (GLS)
Measure of longitudinal shortening as a percentage
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 months
Change in N-terminal pro-B-type natriuretic peptide (NTproBNP) biomarker level.
Measure in blood. Unit pg/ml.
Measured: 12 months
Proportion of patients experiencing cardiovascular hospitalizations.
Measured: 12 months
Proportion of patients experiencing adverse events
Including serious adverse event, grade 3-4 adverse event, adverse reaction, adverse event of special interest.
Measured: 12 months
Proportion of patients discontinuing treatment
Measured: 12 months
Proportion of patients experiencing all-cause mortality.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2024
- Study startJan 2025 (estimated)
- Primary completionApr 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Puerta de Hierro University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Esther Gonzalez López, Puerta de Hierro University Hospital
- Investigators
- Esther Gonzalez Lopez, MD, PhD, Principal investigator, Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06712030
- Sponsor's protocol ID
- 2024-515661-34-00
- Other IDs
- 2024-515661-34-00
- Acronym
- SAVA-TTR
- Status last verified
- Nov 2024
- First submitted
- 19 Nov 2024
- Last updated
- 2 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.