Overview
Sponsor-declared trial summary
Transthyretin cardiac amyloidosis
The primary objective is to determine the impact of treatment with Sacubitril/Valsartan on systolic function in patients with transthyretin amyloid cardiomyopathy and heart failure with reduced ejection fraction, by assessing the change in left ventricular ejection fraction in echocardiogram at 12 months.
Key facts
- Sponsor
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 27 Feb 2025 → ongoing
- Decision date (initial)
- 2024-10-24
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- Instituto de Salud Carlos III (PI23/01180)
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
The primary objective is to determine the impact of treatment with Sacubitril/Valsartan on systolic function in patients with transthyretin amyloid cardiomyopathy and heart failure with reduced ejection fraction, by assessing the change in left ventricular ejection fraction in echocardiogram at 12 months.
Conditions and MedDRA coding
Transthyretin cardiac amyloidosis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 25.1 | LLT | 10087643 | Transthyretin cardiac amyloidosis | 100000004848 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Patients ≥ 18 years of age of both sexes.
- Patients diagnosed with transthyretin amyloid cardiomyopathy, both in its hereditary form (ATTRv) or wild-type form (ATTRwt). The diagnosis of ATTR will be based on histological demonstration of TTR amyloid deposition or non-invasive criteria as indicated in guidelines. For ATTRv diagnosis, demonstration of causal TTR mutation through genetic testing will be required.
- Patients initially evaluated or under follow-up in Cardiomyopathy/Heart Failure/Amyloidosis Units at participating centers.
- Presenting with heart failure and reduced ejection fraction: LVEF ≤45%, in functional class I, II, or III according to the New York Heart Association (NYHA).
Exclusion criteria 9
- 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 <100 mmHg on two consecutive measurements.
- Treatment with ACE inhibitors (IECA), angiotensin II receptor blockers (ARAII), or sacubitril/valsartan at the time of enrollment.
- History of angioedema or hypersensitivity to ACE inhibitors or angiotensin II receptor blockers.
- Treatment with diflunisal.
- Participation in another clinical trial or any condition that, in the investigator's opinion, compromises participation in the study.
- Pregnancy, breastfeeding, or fertile women unwilling to use adequate contraception throughout the study duration.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change in left ventricular ejection fraction (%), assessed by echocardiogram, compared to baseline value after 12-month treatment with Sacubitrl/Valsartan versus management without Sacubitril/Valsartan. An improvement in left ventricular ejection fraction will be defined as an increase of ≥ 5% between the baseline echocardiogram and the 12-month echocardiogram.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Entresto 24 mg/26 mg film-coated tablets
PRD3417298 · Product
- Active substance
- Valsartan
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 194 mg milligram(s)
- Max total dose
- 70810 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- C09DX04 — -
- Marketing authorisation
- EU/1/15/1058/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda
- Sponsor organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda
- Address
- Calle De Joaquin Rodrigo 2
- City
- Majadahonda
- Postcode
- 28222
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda
- Contact name
- Cristina Avendaño Solá
Public contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario Puerta De Hierro Majadahonda
- Contact name
- Cristina Avendaño Solá
Locations
1 EU/EEA country · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 114 | 9 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2025-02-27 | 2025-10-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-515661-34-00 | 1 |
| Protocol (for publication) | D1_protocol ES 2024-515661-34-00 V2 | 2 |
| Protocol (for publication) | Protocol TC V2 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Subject information and informed consent form (for publication) | L1_HIP y CI_version1_sep2024 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC sacubitrilvalsartan | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ENG 2024-515661-34-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ENG 2024-515661-34-00 v2 | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ESP 2024-515661-34-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ESP 2024-515661-34-00 v2 | 2 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-02 | Spain | Acceptable 2024-10-23
|
2024-10-24 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-12-19 | Spain | Acceptable 2026-03-06
|
2026-03-10 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2026-03-10 | Spain | Acceptable | 2026-04-13 |