A Study of LY3540378 in Participants With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)

NCT ID: NCT05592275

Last Updated: 2025-02-12

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

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

335 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-03

Study Completion Date

2025-01-22

Brief Summary

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The main purpose of this study is to assess the efficacy and safety of LY3540378 in adults with worsening heart failure with preserved ejection fraction

Detailed Description

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Conditions

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Heart Failure Heart Failure With Preserved Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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LY3540378 Dose 1

Participants will receive LY3540378 subcutaneously (SC).

Group Type EXPERIMENTAL

LY3540378

Intervention Type DRUG

Administered SC

LY3540378 Dose 2

Participants will receive LY3540378 SC.

Group Type EXPERIMENTAL

LY3540378

Intervention Type DRUG

Administered SC

LY3540378 Dose 3

Participants will receive LY3540378 SC.

Group Type EXPERIMENTAL

LY3540378

Intervention Type DRUG

Administered SC

Placebo

Participants will be given placebo SC.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered SC

Interventions

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LY3540378

Administered SC

Intervention Type DRUG

Placebo

Administered SC

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Experienced an index event, defined as a recent hospitalization for HF requiring ≥1 bolus doses of intravenous diuretics or an out- of- hospital encounter (for example, Emergency Room, clinic visit, infusion clinic, etc.) for HF requiring ≥1 bolus doses of intravenous diuretics.
* Documented LVEF of ≥50% within 12 months prior to screening; as measured by echocardiography, radionuclide ventriculography, invasive angiography, magnetic resonance imaging (MRI), or computerized tomograph (CT).
* Evidence of documentation of LVEF of ≥50% may also include participant medical records, discharge notes or a referral letter from the participant's physician or referring physician that details the participant's medical history.
* Had evidence of clinical HF syndrome consisting of hospitalization for worsening heart failure (WHF) with intravascular volume overload (the index event), as determined by the investigator, based on appropriate supportive documentation at randomization, and defined by ≥2 of the following:

* dyspnea
* jugular venous distention
* pitting edema in lower extremities (\>1+)
* ascites
* pulmonary congestion on chest X-ray
* pulmonary rales AND participant received treatment with IV diuretics.

OR

* Treatment for an urgent visit outside of of being hospitalized with WHF and intravascular volume overload (the index visit) requiring treatment with IV diuretics (defined as ≥2 IV doses) such as in the outpatient setting/emergency room/observation unit/infusion clinic with a clinical response within the past 2 weeks prior to randomization. Urgent visit is defined as an unplanned visit for HF defined by ≥2 of the following:

* dyspnea
* jugular venous distention
* pitting edema in lower extremities (\>1+)
* ascites
* pulmonary rales on lung examination.
* NT-proBNP (\>300 \[sinus rhythm\] or 600 pg/mL \[atrial fibrillation or atrial flutter\] OR BNP (\>100 \[sinus rhythm\] or 200 pg/mL \[atrial fibrillation or atrial flutter\]) at screening.
* eGFR of \>20 mL/min/1.73 m² at V1 (screening; determined by local laboratory), derived from serum creatinine values, age, and sex based on the CKD-EPI equation.

Exclusion Criteria

* Prior documentation of low ventricle ejection fraction (LVEF) ≤45% in the past 12 months.
* Have had acute coronary syndrome or percutaneous coronary intervention, coronary artery bypass graft, cardiac mechanical support implantation, within 3 months prior to V2. (randomization), - or any other cardiac surgery planned during the study.
* Have had left ventricular assist device (LVAD) or cardiac transplantation or have cardiac transplantation planned during the study.
* Have hypertrophic cardiomyopathy (obstructive or nonobstructive), restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac sarcoidosis, known amyloid cardiomyopathy, or inherited cardiomyopathy.
* Have a chronic pulmonary/lung disease (COPD), (pulmonary arterial hypertension, etc) as defined by chronic oxygen dependence. Night-time oxygen is not exclusionary.
* Uncorrected thyroid disease.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Pima Heart

Tucson, Arizona, United States

Site Status

Valley Clinical Trials, Inc.

Covina, California, United States

Site Status

Valley Clinical Trials, Inc.

Northridge, California, United States

Site Status

University of California Irvine Medical Center

Orange, California, United States

Site Status

Pasadena Clinical Research

Pasadena, California, United States

Site Status

Velocity Clinical Research, Coastal Heart Medical Group

Santa Ana, California, United States

Site Status

Excel Medical Clinical Trials

Boca Raton, Florida, United States

Site Status

Infinite Clinical Research

Miami, Florida, United States

Site Status

South Florida Research Solutions - North Flamingo Road

Pembroke Pines, Florida, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Mayo Clinic in Rochester, Minnesota

Rochester, Minnesota, United States

Site Status

University of North Carolina Medical Center

Chapel Hill, North Carolina, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

PharmaTex Research

Amarillo, Texas, United States

Site Status

Baylor Scott & White Health-Advanced Heart and Lung Disease

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

West Houston Area Clinical Trial Consultants

Houston, Texas, United States

Site Status

Texas Institute of Cardiology, PA

McKinney, Texas, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Centro de Investigaciones Metabólicas (CINME)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Site Status

Instituto de Investigaciones Clinicas Zarate

Zárate, Buenos Aires, Argentina

Site Status

Investigaciones Medicas Imoba Srl

Balvanera, Buenos Aires F.D., Argentina

Site Status

Sanatorio Anchorena Recoleta

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Mautalen Salud e Investigación

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Instituto Médico Río Cuarto

Río Cuarto, Córdoba Province, Argentina

Site Status

Hospital Provincial del Centenario

Rosario, Santa Fe Province, Argentina

Site Status

Instituto de Investigaciones Clinicas Rosario

Rosario, Santa Fe Province, Argentina

Site Status

Sanatorio San Martin

Venado Tuerto, Santa Fe Province, Argentina

Site Status

Investigaciones Clínicas Tucumán

San Miguel de Tucumán, Tucumán Province, Argentina

Site Status

CEMEDIC

Buenos Aires, , Argentina

Site Status

Fundación Respirar

Buenos Aires, , Argentina

Site Status

Centro de Investigaciones Clinicas del Litoral

Santa Fe, , Argentina

Site Status

Clínica de Nefrología, Urología y Enfermedades Cardiovasculares

Santa Fe, , Argentina

Site Status

Centro de Pesquisa Silvestre Santé

Rio Branco, Acre, Brazil

Site Status

Universidade Federal de Goias

Goiânia, Goiás, Brazil

Site Status

PUC Trials- Nucleo de Pesquisa clinica da Escola de Medicina da PUCPR

Curitiba, Paraná, Brazil

Site Status

Centro de Pesquisa Clinica do Coracao

Acaraju, Sergipe, Brazil

Site Status

Centro de Pesquisa Sao Lucas

Campinas, São Paulo, Brazil

Site Status

Instituto de Pesquisa clinica de Campinas

Campinas, São Paulo, Brazil

Site Status

Instituto Do Coracao De Marilia

Marília, São Paulo, Brazil

Site Status

CAPED Centro Avancado Pesquisa e Diagnostica

Ribeirão Preto, São Paulo, Brazil

Site Status

Pesquisare Saude

Santo André, São Paulo, Brazil

Site Status

Hospital Santa Paula

São Paulo, São Paulo, Brazil

Site Status

Incor - Instituto do Coracao

São Paulo, São Paulo, Brazil

Site Status

Instituto de Molestias Cardiovasculares de Tatui

Tatuí, São Paulo, Brazil

Site Status

Integral Pesquisa e Ensino

Votuporanga, São Paulo, Brazil

Site Status

Hospital São Lucas de Copacabana

Rio de Janeiro, , Brazil

Site Status

Instituto D'Or Pesquisa e Ensino

Rio de Janeiro, , Brazil

Site Status

SMH Cardiology Clinical Trials

Surrey, British Columbia, Canada

Site Status

Private Practice - Dr. Saul Vizel

Cambridge, Ontario, Canada

Site Status

PACE Cardiology

Newmarket, Ontario, Canada

Site Status

North York Diagnostic and Cardiac Centre

North York, Ontario, Canada

Site Status

Oakville Trafalgar Memorial Hospital

Oakville, Ontario, Canada

Site Status

Heart Health Institute - Scarborough Office

Scarborough Village, Ontario, Canada

Site Status

Medicus MFC Research Clinic

Toronto, Ontario, Canada

Site Status

CPS Research

Waterloo, Ontario, Canada

Site Status

Centre Hospitalier Universite de Sherbrooke - Hôtel-Dieu Hospital

Sherbrooke, Quebec, Canada

Site Status

Fakultní nemocnice Brno Bohunice

Brno, Brno-město, Czechia

Site Status

Fakultni Nemocnice u sv. Anny v Brne

Brno, South Moravian, Czechia

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Site Status

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, Csongrád megye, Hungary

Site Status

Medifarma 98 Kft

Nyíregyháza, Nyíregyháza, Hungary

Site Status

Kistarcsai Flor Ferenc Korhaz

Kistarcsa, Pest County, Hungary

Site Status

Belvárosi Egészségház

Zalaegerszeg, Zala County, Hungary

Site Status

Dél-Pesti Centrumkórház

Budapest, , Hungary

Site Status

Semmelweis University

Budapest, , Hungary

Site Status

Yitzhak Shamir Medical Center

Ẕerifin, Central District, Israel

Site Status

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Site Status

Rambam Health Care Campus

Haifa, Northern District, Israel

Site Status

Sourasky Medical Center

Tel Aviv, Tell Abīb, Israel

Site Status

Kasugai Municipal Hospital

Kasugai, Aichi-ken, Japan

Site Status

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken, Japan

Site Status

Saiseikai Futsukaichi Hospital

Chikushino-shi, Fukuoka, Japan

Site Status

Nakamura Cardiovascular Clinic

Itoshima, Fukuoka, Japan

Site Status

Gunma University Hospital

Maebashi, Gunma, Japan

Site Status

National Hospital Organization Takasaki General Medical Centar

Takasaki, Gunma, Japan

Site Status

Yokohama City University Medical Center

Yokohama, Kanagawa, Japan

Site Status

Yokohama Minami Kyosai Hospital

Yokohama, Kanagawa, Japan

Site Status

Kanagawa Cardiovascular and Respiratory Center

Yokohama, Kanagawa, Japan

Site Status

Minamino Cardiovascular Hospital

Hachiōji, Tokyo, Japan

Site Status

Ome Medical Center

Ōme, Tokyo, Japan

Site Status

Yamanashi Prefectural Central Hospital

Kofu, Yamanashi, Japan

Site Status

Harasanshin Hospital

Fukuoka, , Japan

Site Status

Rakuwakai Otowa Hospital

Kyoto, , Japan

Site Status

National Hospital Organization Okayama Medical Center

Okayama, , Japan

Site Status

Sakurabashi Watanabe Advanced Healthcare Hospital

Osaka, , Japan

Site Status

Yodogawa Christian Hospital

Osaka, , Japan

Site Status

National Hospital Organization - Osaka National Hospital - Institute For Clinical Research

Osaka, , Japan

Site Status

Toyama Prefectural Central Hospital

Toyama, , Japan

Site Status

NZOZ Centrum Medyczne KERmed

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

INTERCOR

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

Private Practice - Dr. Ewa Mirek Bryniarska

Krakow, Lesser Poland Voivodeship, Poland

Site Status

MEDICOME Centrum Badań Klinicznych Oświęcimskie

Oświęcim, Lesser Poland Voivodeship, Poland

Site Status

1 Wojskowy Szpital Kliniczny w Lublinie

Lublin, Lublin Voivodeship, Poland

Site Status

CenterMed Lublin NZOZ

Lublin, Lublin Voivodeship, Poland

Site Status

Balsam Medica

Warsaw, Masovian Voivodeship, Poland

Site Status

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu

Przemyśl, Podkarpackie Voivodeship, Poland

Site Status

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, Podlaskie Voivodeship, Poland

Site Status

KLIMED Marek Klimkiewicz

Bialystok, Podlaskie Voivodeship, Poland

Site Status

SPZOZ Uniwersytecki Szpital Kliniczny Im. Wojskowej Akademii Medycznej UM W Łodzi Centralny Szpital Wetera -T

Lodz, Łódź Voivodeship, Poland

Site Status

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, Łódź Voivodeship, Poland

Site Status

IRMED Osrodek Badan Klinicznych

Piotrkow Trybunalski, Łódź Voivodeship, Poland

Site Status

Provita Profamilia

Piotrkow Trybunalski, Łódź Voivodeship, Poland

Site Status

CHUS - Hospital Clinico Universitario

Santiago de Compostela, A Coruña [La Coruña], Spain

Site Status

Hospital de Denia Marina Salud

Denia, Alicante, Spain

Site Status

Hospital Universitario Reina Sofia

Córdoba, Andalusia, Spain

Site Status

Hospital Universitario Virgen de Valme

Seville, Andalusia, Spain

Site Status

Hospital Germans Trias i Pujol

Badalona, Barcelona [Barcelona], Spain

Site Status

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain

Site Status

Hospital San Juan de la Cruz

Úbeda, Jaén, Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, Murcia, Región de, Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Site Status

Hospital Clinico de Valencia

Valencia, Valenciana, Comunitat, Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Bursa Yüksek İhtisas Eğitim Ve Araştırma Hastanesi

Yıldırım, Bursa, Turkey (Türkiye)

Site Status

Eskisehir Osmangazi University

Eskişehir, Eskişehir, Turkey (Türkiye)

Site Status

Ege Universitesi Hastanesi

Bornova, İzmir, Turkey (Türkiye)

Site Status

Kocaeli Üniversitesi

İzmit, Kocaeli, Turkey (Türkiye)

Site Status

Afyon Kocatepe Üniversitesi Tıp Fakültesi

Afyonkarahisar, , Turkey (Türkiye)

Site Status

Ankara Etlik City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Trakya University Medical Faculty Hospital

Edirne, , Turkey (Türkiye)

Site Status

T.C. Sağlık Bakanlığı İzmir Tepecik Eğitim ve Araştırma Hast

Izmir, , Turkey (Türkiye)

Site Status

Dokuz Eylul Universitesi Hastanesi

Izmir, , Turkey (Türkiye)

Site Status

Mersin University

Mersin, , Turkey (Türkiye)

Site Status

Wycombe General Hospital

High Wycombe, Buckinghamshire, United Kingdom

Site Status

Raigmore Hospital

Inverness, Highland, United Kingdom

Site Status

Northwick Park Hospital

Harrow, London, City of, United Kingdom

Site Status

Glasgow Royal Infirmary

Glasgow, Scotland, United Kingdom

Site Status

West Middlesex University Hospital

Isleworth, , United Kingdom

Site Status

Aintree University Hospital NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Royal Berkshire Hospital

Reading, , United Kingdom

Site Status

Countries

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United States Argentina Brazil Canada Czechia Hungary Israel Japan Poland Spain Turkey (Türkiye) United Kingdom

References

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Borlaug BA, Testani JM, Petrie MC, Wang Z, Cunningham J, Adams KF Jr, Amir O, Belohlavek J, Bocchi E, Freitas A Jr, Hominal M, Kadokami T, Merkely B, Miller CA, Nunez J, Verma S, Yilmaz MB, Oru E, Sam F. Effects of volenrelaxin in worsening heart failure with preserved ejection fraction: a phase 2 randomized trial. Nat Med. 2025 Aug 31. doi: 10.1038/s41591-025-03939-6. Online ahead of print.

Reference Type DERIVED
PMID: 40887551 (View on PubMed)

Related Links

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https://trials.lilly.com/en-US/trial/366076

A Study of LY3540378 in Participants With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)

Other Identifiers

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J3E-MC-EZDB

Identifier Type: OTHER

Identifier Source: secondary_id

2023-505902-40-00

Identifier Type: OTHER

Identifier Source: secondary_id

18473

Identifier Type: -

Identifier Source: org_study_id

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