NCT04803175

Brief Summary

Heart failure (HF) is a chronic disease with weakened heart muscles or abnormal pressure within the heart chambers result in breathlessness, leg edema, or fatigue. A subclass of HF shows reduced heart muscle contractility, which is represented by the left ventricular ejection fraction (LVEF). Valsartan is an angiotensin II receptor blocker, a major drug class for heart failure. Sacubitril/valsartan is a combination of 2 drugs, classified as a new class of drug called angiotensin receptor neprilysin inhibitor (ARNI). Although these medications are both first-line treatment in HF with reduced LVEF, recent guidelines encourage the use of sacubitril/valsartan in patients with ongoing symptoms. After successful treatment, some patients experience recovery of LVEF. In these patients, otherwise called heart failure with improved ejection fraction (HFiEF), it is not clear whether continued treatment with sacubitril/valsartan or valsartan is beneficial in terms of relapse of heart failure or worsening of LVEF. Therefore, the investigators aim to determine whether the treatment with sacubitril/valsartan versus valsartan differs in clinical outcomes after 1 year in HFiEF patients by observing the change in blood test markers of heart failure (N-terminal prohormone of brain natriuretic peptide; NT-proBNP) and aggravation of HF defined as reduced LVEF, congestive symptoms, hospitalization or death from HF.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
100

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Mar 2021

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 25, 2021

Completed
19 days until next milestone

Study Start

First participant enrolled

March 16, 2021

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 17, 2021

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2025

Completed
Last Updated

August 18, 2021

Status Verified

August 1, 2021

Enrollment Period

2.9 years

First QC Date

February 25, 2021

Last Update Submit

August 17, 2021

Conditions

Heart Failure, Systolic

Keywords

Heart Failure with reduced Ejection FractionHeart Failure with improved Ejection FractionSacubitril/valsartanValsartan

Outcome Measures

Primary Outcomes (1)

  • Change in NT-proBNP concentration

    pg/ml

    Baseline, 6 months, 12 months

Secondary Outcomes (4)

  • Heart failure relapse

    6 months and 12 months

  • Hospitalization for heart failure (HHF)

    6 months and 12 months

  • Death caused by heart failure

    6 months and 12 months

  • Mortality

    6 months and 12 months

Other Outcomes (19)

  • left ventricular (LV) ejection fraction (LVEF, percent)

    6 months (optional, personalized) and 12 months

  • LV end-systolic dimension (LVESD, mm)

    6 months (optional, personalized) and 12 months

  • LV end-diastolic dimension (LVEDD, mm)

    6 months (optional, personalized) and 12 months

  • +16 more other outcomes

Study Arms (2)

Sacubitril/valsartan

Patients undergoing continued treatment with sacubitril/valsartan after improvement of LVEF \>40% with \> 3 months of sacubitril/valsartan treatment. Dose and titration schedule will be individualized by discretion of the attending physician.

Drug: Sacubitril-Valsartan

Valsartan

Patients undergoing continued treatment with valsartan after improvement of LVEF \>40% with \> 3 months of sacubitril/valsartan treatment. Dose and titration schedule will be individualized by discretion of the attending physician.

Drug: Valsartan

Interventions

Sacubitril-ValsartanDRUG

Participants will receive individualized dosage and titration as part of routine medical care, and a the effect will be studied for at least 12 months. The investigator does not assign specific interventions to the study participants.

Also known as: Entresto
Sacubitril/valsartan
ValsartanDRUG

Participants will receive individualized dosage and titration as part of routine medical care, and a the effect will be studied for at least 12 months. The investigator does not assign specific interventions to the study participants.

Also known as: Diovan
Valsartan

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

1. Consecutive participant sampling was done for all eligible patients. 2. Patients visiting a specialized heart failure clinic at one of the top tertiary level hospitals in Seoul, Korea. Patients have a nationwide distribution geographically, and show a wide range of clinical presentations.

You may qualify if:

  • Patient with a history of HF with reduced EF (HFrEF; LVEF \<40 percent) and received treatment with sacubitril/valsartan for at least 3 months, after which showing improvement of LVEF to \>40 percent and symptoms of NYHA functional class I or II
  • serum NT-proBNP levels \< 400 pg/dL for sinus rhythm and \< 600pg/dL for atrial fibrillation
  • Patients on stable doses of diuretics for 1 week

You may not qualify if:

  • History of hospitalization for heart failure within 30 days before enrollment
  • History of acute coronary syndrome (acute myocardial infarction or unstable angina), percutaneous coronary artery intervention or cardiac surgery within 30 days before enrollment
  • History of cardiac resynchronization therapy within 90 days before screening
  • Planned percutaneous or surgical coronary artery revascularization, or major cardiac surgery (coronary artery bypass, valvuloplasty, mechanical cardiac support or heart transplantation) within 90 days after enrollment
  • Contraindicated or has history of hypersensitivity to RAS blockers including ACEI or ARB
  • Use of inotropes
  • Survival estimate \< 3months
  • Otherwise deemed as inappropriate by the attending physician

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Related Publications (4)

  • Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S, Jackson R, Rahneva T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu JN, Pantazis A, Cook SA, Ware JS, Baksi AJ, Pennell DJ, Rosen SD, Cowie MR, Cleland JGF, Prasad SK. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019 Jan 5;393(10166):61-73. doi: 10.1016/S0140-6736(18)32484-X. Epub 2018 Nov 11.

    PMID: 30429050BACKGROUND

  • Januzzi JL Jr, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K, Camacho A, Pina IL, Rocha RA, Shah AM, Williamson KM, Solomon SD; PROVE-HF Investigators. Association of Change in N-Terminal Pro-B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction. JAMA. 2019 Sep 17;322(11):1085-1095. doi: 10.1001/jama.2019.12821.

    PMID: 31475295BACKGROUND

  • Wilcox JE, Fang JC, Margulies KB, Mann DL. Heart Failure With Recovered Left Ventricular Ejection Fraction: JACC Scientific Expert Panel. J Am Coll Cardiol. 2020 Aug 11;76(6):719-734. doi: 10.1016/j.jacc.2020.05.075.

    PMID: 32762907BACKGROUND

  • Bak M, Park Y, Kim D, Shin H, Hong D, Yang JH, Choi JO. Angiotensin receptor blocker versus angiotensin receptor-neprilysin inhibitor in improved HF with stabilized NT-proBNP levels. Rev Esp Cardiol (Engl Ed). 2025 Dec 11:S1885-5857(25)00350-0. doi: 10.1016/j.rec.2025.12.006. Online ahead of print. English, Spanish.

    PMID: 41390047DERIVED

MeSH Terms

Conditions

Heart Failure, Systolic

Interventions

sacubitril and valsartan sodium hydrate drug combinationValsartan

Condition Hierarchy (Ancestors)

Heart FailureHeart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

TetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsValineAmino Acids, Branched-ChainAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Essential

Central Study Contacts

Jinoh Choi, MD, PhD

CONTACT

82234103417choijean5@gmail.com

Yoonjee Park, MD

CONTACT

821026729748yoonjeedrpark@gmail.com

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Target Duration
12 Months
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute

Study Record Dates

First Submitted

February 25, 2021

First Posted

March 17, 2021

Study Start

March 16, 2021

Primary Completion

February 1, 2024

Study Completion

February 1, 2025

Last Updated

August 18, 2021

Record last verified: 2021-08

Locations

KR(1)