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

NCT ID: NCT06712030

Last Updated: 2024-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-31

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The analysis of the echocardiogram will be performed by evaluators blinded to the treatment and the timing of the imaging.

Study Groups

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Sacubitril/Valsartan

Sacubitril/valsartan up to maximum tolerated dose

Group Type EXPERIMENTAL

Sacubitril / Valsartan

Intervention Type DRUG

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

No treatment

No initiation of Sacubitril/valsartan

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Sacubitril / Valsartan

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Puerta de Hierro University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Esther Gonzalez López

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Esther Gonzalez Lopez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Site Status

Countries

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Spain

Central Contacts

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Esther Gonzalez Lopez, MD, PhD

Role: CONTACT

+34 91 1916000

Facility Contacts

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Esther Gonzalez Lopez, MD, PhD

Role: primary

+34 91 1916000

Noemí Ramos López

Role: backup

Other Identifiers

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2024-515661-34-00

Identifier Type: CTIS

Identifier Source: secondary_id

2024-515661-34-00

Identifier Type: -

Identifier Source: org_study_id