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

Phase 2
Terminated
Conditions
Heart Failure
Heart Failure With Preserved Ejection Fraction
Interventions
Drug: Placebo
Registration Number
NCT05592275
Lead Sponsor
Eli Lilly and Company
Brief Summary

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

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
335
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.
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will be given placebo SC.
LY3540378 Dose 1LY3540378Participants will receive LY3540378 subcutaneously (SC).
LY3540378 Dose 2LY3540378Participants will receive LY3540378 SC.
LY3540378 Dose 3LY3540378Participants will receive LY3540378 SC.
Primary Outcome Measures
NameTimeMethod
Change from Baseline in Left Atrial Reservoir Strain (LARS)Baseline, Week 26
Secondary Outcome Measures
NameTimeMethod
Change from Baseline in cystatin-CBaseline, Week 26
Change from Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)Baseline, Week 26
Change from Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI)Baseline, Week 26
Change from Baseline Left Atrial End-Systolic Volume Index (LAESVI)Baseline, Week 26
Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)Baseline, Week 26

eGFR calculated by creatinine and cystatin C

Change from Baseline in Serum CreatinineBaseline, Week 26

Trial Locations

Locations (136)

Pima Heart

🇺🇸

Tucson, Arizona, United States

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

Pasadena Clinical Research

🇺🇸

Pasadena, California, United States

Mayo Clinic in Rochester, Minnesota

🇺🇸

Rochester, Minnesota, United States

University of North Carolina Medical Center

🇺🇸

Chapel Hill, North Carolina, United States

Abington Memorial Hospital

🇺🇸

Abington, Pennsylvania, United States

PharmaTex Research

🇺🇸

Amarillo, Texas, United States

University of Texas Medical Branch

🇺🇸

Galveston, Texas, United States

University of California Irvine Medical Center

🇺🇸

Orange, California, United States

Velocity Clinical Research, Coastal Heart Medical Group

🇺🇸

Santa Ana, California, United States

Infinite Clinical Research

🇺🇸

Miami, Florida, United States

South Florida Research Solutions - North Flamingo Road

🇺🇸

Pembroke Pines, Florida, United States

University Medical Center New Orleans

🇺🇸

New Orleans, Louisiana, United States

Excel Medical Clinical Trials

🇺🇸

Boca Raton, Florida, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Baylor Scott & White Health-Advanced Heart and Lung Disease

🇺🇸

Dallas, Texas, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

West Houston Area Clinical Trial Consultants

🇺🇸

Houston, Texas, United States

Texas Institute of Cardiology, PA

🇺🇸

McKinney, Texas, United States

University of Wisconsin Hospital and Clinics

🇺🇸

Madison, Wisconsin, United States

Centro de Investigaciones Metabólicas (CINME)

🇦🇷

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Zarate

🇦🇷

Zárate, Buenos Aires, Argentina

Centro de Investigaciones Clinicas del Litoral

🇦🇷

Santa Fe, Argentina

Clínica de Nefrología, Urología y Enfermedades Cardiovasculares

🇦🇷

Santa Fe, Argentina

Investigaciones Medicas Imoba Srl

🇦🇷

Balvanera, Ciudad Autónoma De Buenos Aires, Argentina

Sanatorio Anchorena Recoleta

🇦🇷

Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Mautalen Salud e Investigación

🇦🇷

Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Instituto Médico Río Cuarto

🇦🇷

Río Cuarto, Córdoba, Argentina

Hospital Provincial del Centenario

🇦🇷

Rosario, Santa Fe, Argentina

Instituto de Investigaciones Clinicas Rosario

🇦🇷

Rosario, Santa Fe, Argentina

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

🇦🇷

Ciudad Autonoma de Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Sanatorio San Martin

🇦🇷

Venado Tuerto, Santa Fe, Argentina

Centro de Pesquisa Silvestre Santé

🇧🇷

Rio Branco, Acre, Brazil

Investigaciones Clínicas Tucumán

🇦🇷

San Miguel de Tucuman, Tucumán, Argentina

CEMEDIC

🇦🇷

Buenos Aires, Argentina

Fundación Respirar

🇦🇷

Buenos Aires, Argentina

Universidade Federal de Goias

🇧🇷

Goiania, Goiás, Brazil

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

🇧🇷

Curitiba, Paraná, Brazil

Centro de Pesquisa Clinica do Coracao

🇧🇷

Acaraju, Sergipe, Brazil

Centro de Pesquisa Sao Lucas

🇧🇷

Campinas, São Paulo, Brazil

Instituto de Pesquisa clinica de Campinas

🇧🇷

Campinas, São Paulo, Brazil

Instituto Do Coracao De Marilia

🇧🇷

Marilia, São Paulo, Brazil

CAPED Centro Avancado Pesquisa e Diagnostica

🇧🇷

Ribeirao Preto, São Paulo, Brazil

Pesquisare Saude

🇧🇷

Santo André, São Paulo, Brazil

Hospital Santa Paula

🇧🇷

Sao Paulo, São Paulo, Brazil

Incor - Instituto do Coracao

🇧🇷

Sao Paulo, São Paulo, Brazil

Instituto de Molestias Cardiovasculares de Tatui

🇧🇷

Tatui, São Paulo, Brazil

Integral Pesquisa e Ensino

🇧🇷

Votuporanga, São Paulo, Brazil

Hospital São Lucas de Copacabana

🇧🇷

Rio de Janeiro, Brazil

Instituto D'Or Pesquisa e Ensino

🇧🇷

Rio de Janeiro, Brazil

SMH Cardiology Clinical Trials

🇨🇦

Surrey, British Columbia, Canada

Private Practice - Dr. Saul Vizel

🇨🇦

Cambridge, Ontario, Canada

PACE Cardiology

🇨🇦

Newmarket, Ontario, Canada

North York Diagnostic and Cardiac Centre

🇨🇦

North York, Ontario, Canada

Oakville Trafalgar Memorial Hospital

🇨🇦

Oakville, Ontario, Canada

Heart Health Institute - Scarborough Office

🇨🇦

Scarborough, Ontario, Canada

Medicus MFC Research Clinic

🇨🇦

Toronto, Ontario, Canada

CPS Research

🇨🇦

Waterloo, Ontario, Canada

Centre Hospitalier Universite de Sherbrooke - Hôtel-Dieu Hospital

🇨🇦

Sherbrooke, Quebec, Canada

Fakultní nemocnice Brno Bohunice

🇨🇿

Brno, Brno-město, Czechia

Fakultni Nemocnice u sv. Anny v Brne

🇨🇿

Brno, Jihomoravský Kraj, Czechia

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha 2, Czechia

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

🇭🇺

Szeged, Csongrád, Hungary

Medifarma 98 Kft

🇭🇺

Nyiregyhaza, Nyíregyháza, Hungary

Kistarcsai Flor Ferenc Korhaz

🇭🇺

Kistarcsa, Pest, Hungary

Belvárosi Egészségház

🇭🇺

Zalaegerszeg, Zala, Hungary

Dél-Pesti Centrumkórház

🇭🇺

Budapest, Hungary

Semmelweis University

🇭🇺

Budapest, Hungary

Yitzhak Shamir Medical Center

🇮🇱

Zerifin, HaMerkaz, Israel

Rambam Health Care Campus

🇮🇱

Haifa, HaTsafon, Israel

Sourasky Medical Center

🇮🇱

Tel Aviv, Tell Abīb, Israel

Hadassah Medical Center

🇮🇱

Jerusalem, Yerushalayim, Israel

Kasugai Municipal Hospital

🇯🇵

Kasugai, Aichi, Japan

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

🇯🇵

Nagoya, Aichi, Japan

Saiseikai Futsukaichi Hospital

🇯🇵

Chikushino, Fukuoka, Japan

Nakamura Cardiovascular Clinic

🇯🇵

Itoshima, Fukuoka, Japan

Gunma University Hospital

🇯🇵

Maebashi, Gunma, Japan

National Hospital Organization Takasaki General Medical Centar

🇯🇵

Takasaki, Gunma, Japan

Yokohama City University Medical Center

🇯🇵

Yokohama, Kanagawa, Japan

Yokohama Minami Kyosai Hospital

🇯🇵

Yokohama, Kanagawa, Japan

Kanagawa Cardiovascular and Respiratory Center

🇯🇵

Yokohama, Kanagawa, Japan

Minamino Cardiovascular Hospital

🇯🇵

Hachioji, Tokyo, Japan

Ome Medical Center

🇯🇵

Ome, Tokyo, Japan

Yamanashi Prefectural Central Hospital

🇯🇵

Kofu, Yamanashi, Japan

Harasanshin Hospital

🇯🇵

Fukuoka, Japan

Rakuwakai Otowa Hospital

🇯🇵

Kyoto, Japan

National Hospital Organization Okayama Medical Center

🇯🇵

Okayama, Japan

Sakurabashi Watanabe Advanced Healthcare Hospital

🇯🇵

Osaka, Japan

Yodogawa Christian Hospital

🇯🇵

Osaka, Japan

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

🇯🇵

Osaka, Japan

Toyama Prefectural Central Hospital

🇯🇵

Toyama, Japan

NZOZ Centrum Medyczne KERmed

🇵🇱

Bydgoszcz, Kujawsko-pomorskie, Poland

Hospital de Denia Marina Salud

🇪🇸

Dénia, Alicante, Spain

Hospital Universitario Reina Sofia

🇪🇸

Cordoba, Andalucía, Spain

Hospital Universitario Virgen de Valme

🇪🇸

Sevilla, Andalucía, Spain

Hospital Germans Trias i Pujol

🇪🇸

Badalona, Barcelona [Barcelona], Spain

Hospital Universitari de Bellvitge

🇪🇸

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

Hospital San Juan de la Cruz

🇪🇸

Ubeda, Jaén, Spain

Hospital Universitario Ramón y Cajal

🇪🇸

Madrid, Madrid, Comunidad De, Spain

INTERCOR

🇵🇱

Bydgoszcz, Kujawsko-pomorskie, Poland

CenterMed Lublin NZOZ

🇵🇱

Lublin, Lubelskie, Poland

Uniwersytecki Szpital Kliniczny w Białymstoku

🇵🇱

Białystok, Podlaskie, Poland

1 Wojskowy Szpital Kliniczny w Lublinie

🇵🇱

Lublin, Lubelskie, Poland

Balsam Medica

🇵🇱

Warsaw, Mazowieckie, Poland

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu

🇵🇱

Przemysl, Podkarpackie, Poland

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

🇵🇱

Łódź, Łódzkie, Poland

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

🇵🇱

Łódź, Łódzkie, Poland

CHUS - Hospital Clinico Universitario

🇪🇸

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

Private Practice - Dr. Ewa Mirek Bryniarska

🇵🇱

Krakow, Małopolskie, Poland

MEDICOME Centrum Badań Klinicznych Oświęcimskie

🇵🇱

Oświęcim, Małopolskie, Poland

KLIMED Marek Klimkiewicz

🇵🇱

Białystok, Podlaskie, Poland

IRMED Osrodek Badan Klinicznych

🇵🇱

Piotrkow Trybunalski, Łódzkie, Poland

Provita Profamilia

🇵🇱

Piotrków Trybunalski, Łódzkie, Poland

Hospital Clínico Universitario Virgen de la Arrixaca

🇪🇸

El Palmar, Murcia, Murcia, Región De, Spain

Hospital Universitario Virgen de la Victoria

🇪🇸

Malaga, Málaga, Spain

Hospital Clinico de Valencia

🇪🇸

Valencia, Valenciana, Comunitat, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Bursa Yüksek İhtisas Eğitim Ve Araştırma Hastanesi

🇹🇷

Yıldırım, Bursa, Turkey

Eskisehir Osmangazi University

🇹🇷

Eskisehir, Eskişehir, Turkey

Ege Universitesi Hastanesi

🇹🇷

Bornova, İzmir, Turkey

Kocaeli Üniversitesi

🇹🇷

Izmit, Kocaeli, Turkey

Afyon Kocatepe Üniversitesi Tıp Fakültesi

🇹🇷

Afyonkarahisar, Turkey

Ankara Etlik City Hospital

🇹🇷

Ankara, Turkey

Trakya University Medical Faculty Hospital

🇹🇷

Edirne, Turkey

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

🇹🇷

Izmir, Turkey

Dokuz Eylul Universitesi Hastanesi

🇹🇷

Izmir, Turkey

Mersin University

🇹🇷

Mersin, Turkey

Wycombe General Hospital

🇬🇧

High Wycombe, Buckinghamshire, United Kingdom

Raigmore Hospital

🇬🇧

Inverness, Highland, United Kingdom

Northwick Park Hospital

🇬🇧

Harrow, London, City Of, United Kingdom

Glasgow Royal Infirmary

🇬🇧

Glasgow, Scotland, United Kingdom

West Middlesex University Hospital

🇬🇧

Isleworth, United Kingdom

Aintree University Hospital NHS Foundation Trust

🇬🇧

Liverpool, United Kingdom

Wythenshawe Hospital

🇬🇧

Manchester, United Kingdom

Royal Berkshire Hospital

🇬🇧

Reading, United Kingdom

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