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

Heart Failure Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of LY3540378 in Adults With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05592275
• Other study ID #: 18473
• Secondary ID: J3E-MC-EZDB2023-
• Status: Recruiting
• Phase: Phase 2
• Start date: February 3, 2023
• Est. completion date: January 2026

Study information

• Verified date: June 2024
• Source: Eli Lilly and Company
• Contact: There may be multiple sites in this clinical trial. 1-877-CTLILL
• Phone: 1-317-615-4559
• Email: ClinicalTrials.gov[@]lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 432
• Est. completion date: January 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Prior chronic treatment, or prescription, with a loop diuretic (for example, furosemide, torsemide, bumetanide) for =30 days prior to the index event. Medical records, discharge notes and physician referral letters may serve as documentation for prior chronic treatment with a loop diuretic.

• Experienced an index event, defined as a recent hospitalization for HF requiring =2 bolus doses of intravenous diuretics or an out- of- hospital encounter (for example, Emergency Room, clinic visit, infusion clinic, etc.) for HF requiring =2 bolus doses of intravenous diuretics.

• Chronic HF diagnosed for at least 3 months before V1 (screening)

• 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 900 picograms/milliliter (pg/mL) [atrial fibrillation or atrial flutter] OR brain natriuretic (BNP) (>100 [sinus rhythm] or 300 pg/mL [atrial fibrillation or atrial flutter]) at screening.

Note: The presence or absence of atrial fibrillation or atrial flutter to determine the appropriate cut-off for a given BNP or NT-proBNP sample should be evaluated using electrocardiogram (ECG) performed at screening prior to the collection of the BNP or NT-proBNP sample.

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 day 2. (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 severe chronic obstructive pulmonary disease (COPD), (pulmonary arterial hypertension, etc) as defined by chronic oxygen dependence. Night-time oxygen is not exclusionary.

• Uncorrected thyroid disease.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• LY3540378
Administered SC
• Placebo
Administered SC

Locations

Country	Name	City	State
Argentina	Investigaciones Medicas Imoba Srl	Balvanera	Ciudad Autónoma De Buenos Aire
Argentina	CEMEDIC	Buenos Aires
Argentina	Fundación Respirar	Buenos Aires
Argentina	Mautalen Salud e Investigación	Buenos Aires	Ciudad Autónoma De Buenos Aires
Argentina	Centro de Investigaciones Metabólicas (CINME)	Ciudad Autónoma de Buenos Aire	Buenos Air
Argentina	Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada	Ciudad Autonoma de 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	Investigaciones Clínicas Tucumán	San Miguel de Tucuman	Tucumán
Argentina	Centro de Investigaciones Clinicas del Litoral	Santa Fe
Argentina	Clínica de Nefrología, Urología y Enfermedades Cardiovasculares	Santa Fe
Argentina	Sanatorio San Martin	Venado Tuerto	Santa Fe
Argentina	Instituto de Investigaciones Clinicas Zarate	Zárate	Buenos Aires
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	PUC Trials- Nucleo de Pesquisa clinica da Escola de Medicina da PUCPR	Curitiba	Paraná
Brazil	Universidade Federal de Goias	Goiania	Goiás
Brazil	Instituto Do Coracao De Marilia	Marilia	São Paulo
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	CAPED Centro Avancado Pesquisa e Diagnostica	Ribeirao Preto	São Paulo
Brazil	Centro de Pesquisa Silvestre Santé	Rio Branco	Acre
Brazil	Hospital São Lucas de Copacabana	Rio de Janeiro
Brazil	Instituto D'Or Pesquisa e Ensino	Rio de Janeiro
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
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	Centre Hospitalier Universite de Sherbrooke - Hôtel-Dieu Hospital	Sherbrooke	Quebec
Canada	SMH Cardiology Clinical Trials	Surrey	British Columbia
Canada	Medicus MFC Research Clinic	Toronto	Ontario
Canada	CPS Research	Waterloo	Ontario
Czechia	Fakultní nemocnice Brno Bohunice	Brno	Brno-mesto
Czechia	Fakultni Nemocnice u sv. Anny v Brne	Brno	Jihomoravský Kraj
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Hungary	Dél-Pesti Centrumkórház	Budapest
Hungary	Semmelweis University	Budapest
Hungary	Flor Ferenc Hospital of Pest County	Kistarcsa	Pest
Hungary	Medifarma 98 Kft	Nyiregyhaza	Nyíregyháza
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ	Szeged	Csongrád
Hungary	Belvárosi Egészségház	Zalaegerszeg	Zala
Israel	Rambam Health Care Campus	Haifa	HaTsafon
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Sourasky Medical Center	Tel Aviv	Tell Abib
Israel	Yitzhak Shamir Medical Center	Zerifin	HaMerkaz
Japan	Saiseikai Futsukaichi Hospital	Chikushino	Fukuoka
Japan	Harasanshin Hospital	Fukuoka
Japan	Minamino Cardiovascular Hospital	Hachioji	Tokyo
Japan	Nakamura Cardiovascular Clinic	Itoshima	Fukuoka
Japan	Kasugai Municipal Hospital	Kasugai	Aichi
Japan	Yamanashi Prefectural Central Hospital	Kofu	Yamanashi
Japan	Rakuwakai Otowa Hospital	Kyoto
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	Japanese Red Cross Nagoya Daini Hospital	Nagoya	Aichi
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Ome Municipal General Hospital	Ome	Tokyo
Japan	National Hospital Organization - Osaka National Hospital - Institute For Clinical Research	Osaka
Japan	Sakurabashi Watanabe Hospital	Osaka
Japan	Yodogawa Christian Hospital	Osaka
Japan	National Hospital Organization Takasaki General Medical Centar	Takasaki	Gunma
Japan	Toyama Prefectural Central Hospital	Toyama
Japan	Kanagawa Cardiovascular and Respiratory Center	Yokohama	Kanagawa
Japan	Yokohama City University Medical Center	Yokohama	Kanagawa
Japan	Yokohama Minami Kyosai Hospital	Yokohama	Kanagawa
Poland	KLIMED Marek Klimkiewicz	Bialystok	Podlaskie
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok	Podlaskie
Poland	INTERCOR	Bydgoszcz	Kujawsko-pomorskie
Poland	NZOZ Centrum Medyczne KERmed	Bydgoszcz	Kujawsko-pomorskie
Poland	Private Practice - Dr. Ewa Mirek Bryniarska	Krakow	Malopolskie
Poland	SPZOZ Uniwersytecki Szpital Kliniczny Im. Wojskowej Akademii Medycznej UM W Lodzi Centralny Szpital Wetera -T	Lódz	Lódzkie
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lódz	Lódzkie
Poland	1 Wojskowy Szpital Kliniczny w Lublinie	Lublin	Lubelskie
Poland	CenterMed Lublin NZOZ	Lublin	Lubelskie
Poland	MEDICOME Centrum Badan Klinicznych Oswiecimskie	Oswiecim	Malopolskie
Poland	IRMED Osrodek Badan Klinicznych	Piotrkow Trybunalski	Lódzkie
Poland	Provita Profamilia	Piotrkow Trybunalski	Lódzkie
Poland	Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu	Przemysl	Podkarpackie
Poland	Balsam Medica	Warsaw	Mazowieckie
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona [Barcelona]
Spain	Hospital Universitario Reina Sofia	Cordoba	Andalucía
Spain	Hospital de Denia Marina Salud	Dénia	Alicante
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	El Palmar, Murcia	Murcia, Región De
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Catalunya [Cataluña]
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Virgen de la Victoria	Malaga	Málaga
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [La Coruña]
Spain	Hospital Universitario Virgen de Valme	Sevilla	Andalucía
Spain	Hospital San Juan de la Cruz	Ubeda	Jaén
Spain	Hospital Clinico de Valencia	Valencia	Valenciana, Comunitat
Turkey	Afyon Kocatepe Üniversitesi Tip Fakültesi	Afyonkarahisar
Turkey	Ankara Etlik City Hospital	Ankara
Turkey	Ege Universitesi Hastanesi	Bornova	Izmir
Turkey	Trakya University	Edirne
Turkey	Eskisehir Osmangazi University	Eskisehir	Eskisehir
Turkey	Dokuz Eylul Universitesi Hastanesi	Izmir
Turkey	Kocaeli Üniversitesi	Kocaeli
Turkey	Mersin University	Mersin
Turkey	Bursa Yüksek Ihtisas Egitim Ve Arastirma Hastanesi	Yildirim	Bursa
United Kingdom	Glasgow Royal Infirmary	Glasgow	Scotland
United Kingdom	Northwick Park Hospital	Harrow	London, City Of
United Kingdom	Wycombe General Hospital	High Wycombe	Buckinghamshire
United Kingdom	Raigmore Hospital	Inverness	Highland
United Kingdom	Aintree University Hospital NHS Foundation Trust	Liverpool
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Royal Berkshire Hospital	Reading
United States	PharmaTex Research	Amarillo	Texas
United States	Excel Medical Clinical Trials	Boca Raton	Florida
United States	Boston Medical Center	Boston	Massachusetts
United States	University of North Carolina Medical Center	Chapel Hill	North Carolina
United States	Valley Clinical Trials, Inc.	Covina	California
United States	Baylor Scott & White Health-Advanced Heart and Lung Disease	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Texas Medical Branch	Galveston	Texas
United States	West Houston Area Clinical Trial Consultants	Houston	Texas
United States	University of Wisconsin Hospitals and Clinics	Madison	Wisconsin
United States	Texas Institute of Cardiology, PA	McKinney	Texas
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Pasadena Clinical Research	Pasadena	California
United States	South Florida Research Solutions - North Flamingo Road	Pembroke Pines	Florida
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	Velocity Clinical Research, Coastal Heart Medical Group	Santa Ana	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Czechia,  Hungary,  Israel,  Japan,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Left Atrial Reservoir Strain (LARS)		Baseline, Week 26
Secondary	Change from Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)		Baseline, Week 26
Secondary	Change from Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI)		Baseline, Week 26
Secondary	Change from Baseline Left Atrial End-Systolic Volume Index (LAESVI)		Baseline, Week 26
Secondary	Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)	eGFR calculated by creatinine and cystatin C	Baseline, Week 26
Secondary	Change from Baseline in Serum Creatinine		Baseline, Week 26
Secondary	Change from Baseline in cystatin-C		Baseline, Week 26

External Links

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