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

NCT06712030 | Not Yet Recruiting Phase 3

• 1 other identifier: 2024-515661-34-00
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief 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%). 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.

Conditions

Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)

Keywords

Heart failure; Reduced ejection fraction; Angiotensin receptor/neprilysin inhibitors; Sacubitril valsartan

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular systolic function (%) assessed by echocardiogram.

  Measured by biplane method in percentage

  12 months

Secondary Outcomes (9)

• Change in left ventricular systolic function assessed by global longitudinal strain (GLS)

  12 months

• Change in E/e' ratio measured by echocardiogram.

  12 months

• Change in functional capacity assessed by 6-minute walk test

  12 months

• Change in quality of life according to the Kansas City Cardiomyopathy Questionnaire

  12 months

• Change in N-terminal pro-B-type natriuretic peptide (NTproBNP) biomarker level.

  12 months

Study Arms (2)

Sacubitril/Valsartan

EXPERIMENTAL

Sacubitril/valsartan up to maximum tolerated dose

Drug: Sacubitril / Valsartan

No treatment

NO INTERVENTION

No initiation of Sacubitril/valsartan

Interventions

Sacubitril / Valsartan DRUG

Dose titration of Sacubitril/Valsartán to the maximum tolerated dose (maximum 97/103 mg)

Sacubitril/Valsartan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Puerta de Hierro University Hospital: lead

Study Sites (1)

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Esther Gonzalez Lopez, MD, PhD

  Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, IDIPHISA, Madrid, Spain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Esther Gonzalez Lopez, MD, PhD

CONTACT

+34 91 1916000; egonzalezlopez@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The analysis of the echocardiogram will be performed by evaluators blinded to the treatment and the timing of the imaging.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: December 2, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After study scientific publication
• Access Criteria: Under request to Study Chair

Locations

ES (1)