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

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)

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

Study Overview

• Status: Terminated
• Conditions: Heart Failure; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Placebo; Drug: LY3540378

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1407
    • CEMEDIC
  • Buenos Aires, Argentina, C1426ABP
    • Fundación Respirar
  • Santa Fe, Argentina, 3000
    • Clínica de Nefrología, Urología y Enfermedades Cardiovasculares
  • Santa Fe, Argentina, 3000
    • Centro de Investigaciones Clinicas del Litoral
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1056ABI
      • Centro de Investigaciones Metabólicas (CINME)
    • Zárate, Buenos Aires, Argentina, B2800DGH
      • Instituto de Investigaciones Clinicas Zarate
  • Buenos Aires F.D.
    • Balvanera, Buenos Aires F.D., Argentina, C1056ABH
      • Investigaciones Medicas IMOBA SRL
    • Buenos Aires, Buenos Aires F.D., Argentina, C1425AGC
      • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
    • Buenos Aires, Buenos Aires F.D., Argentina, C1128AAF
      • Mautalen Salud e Investigación
    • Buenos Aires, Buenos Aires F.D., Argentina, 1425
      • Sanatorio Anchorena Recoleta
  • Córdoba Province
    • Río Cuarto, Córdoba Province, Argentina, 5800
      • Instituto Medico Rio Cuarto
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2002
      • Hospital Provincial del Centenario
    • Rosario, Santa Fe Province, Argentina, S2000CVD
      • Instituto de Investigaciones Clinicas Rosario
    • Venado Tuerto, Santa Fe Province, Argentina, 2600
      • Sanatorio San Martin
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Investigaciones Clinicas Tucuman
• Brazil
  • Rio de Janeiro, Brazil, 22061-080
    • Hospital São Lucas de Copacabana
  • Rio de Janeiro, Brazil, 22281-100
    • Instituto D'Or Pesquisa e Ensino
  • Acre
    • Rio Branco, Acre, Brazil, 69915-030
      • Centro de Pesquisa Silvestre Santé
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-020
      • Universidade Federal de Goias
  • Paraná
    • Curitiba, Paraná, Brazil, 80230-130
      • PUC Trials- Nucleo de Pesquisa clinica da Escola de Medicina da PUCPR
  • Sergipe
    • Acaraju, Sergipe, Brazil, 49055-530
      • Centro de Pesquisa Clínica do Coração
  • São Paulo
    • Campinas, São Paulo, Brazil, 13060-080
      • Instituto de Pesquisa clinica de Campinas
    • Campinas, São Paulo, Brazil, 13034-685
      • Centro de Pesquisa Sao Lucas
    • Marília, São Paulo, Brazil, 17515-000
      • Instituto do Coracao de Marilia
    • Ribeirão Preto, São Paulo, Brazil, 14026-900
      • CAPED Centro Avancado Pesquisa e Diagnostica
    • Santo André, São Paulo, Brazil, 09080-110
      • Pesquisare Saude
    • São Paulo, São Paulo, Brazil, 04556-100
      • Hospital Santa Paula
    • São Paulo, São Paulo, Brazil, 05403-900
      • Incor - Instituto do Coracao
    • Tatuí, São Paulo, Brazil, 18270-170
      • Instituto de Molestias Cardiovasculares de Tatui
    • Votuporanga, São Paulo, Brazil, 15501-405
      • Integral Pesquisa e Ensino
• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • SMH Cardiology Clinical Trials
  • Ontario
    • Cambridge, Ontario, Canada, N1R 7R1
      • Private Practice - Dr. Saul Vizel
    • Newmarket, Ontario, Canada, L3Y 2P6
      • PACE Cardiology
    • North York, Ontario, Canada, M6B 3H7
      • North York Diagnostic and Cardiac Centre
    • Oakville, Ontario, Canada, L6M 1M1
      • Oakville Trafalgar Memorial Hospital
    • Scarborough Village, Ontario, Canada, M1B 4Z8
      • Heart Health Institute - Scarborough Office
    • Toronto, Ontario, Canada, M4P 1E4
      • Medicus MFC Research Clinic
    • Waterloo, Ontario, Canada, N2T 0C1
      • CPS Research
  • Quebec
    • Sherbrooke, Quebec, Canada, J1G 2E8
      • Centre Hospitalier Universite de Sherbrooke - Hôtel-Dieu Hospital
• Czechia
  • Prague, Czechia, 12808
    • Vseobecna fakultni nemocnice v Praze
  • Brno-město
    • Brno, Brno-město, Czechia, 62500
      • Fakultní nemocnice Brno Bohunice
  • South Moravian
    • Brno, South Moravian, Czechia, 60200
      • Fakultni nemocnice u sv. Anny v Brne
• Hungary
  • Budapest, Hungary, 1122
    • Semmelweis University
  • Budapest, Hungary, 1097
    • Dél-Pesti Centrumkórház
  • Csongrád megye
    • Szeged, Csongrád megye, Hungary, 6720
      • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
  • Nyíregyháza
    • Nyíregyháza, Nyíregyháza, Hungary, 4400
      • Medifarma 98 Kft
  • Pest County
    • Kistarcsa, Pest County, Hungary, 2143
      • Kistarcsai Flor Ferenc Korhaz
  • Zala County
    • Zalaegerszeg, Zala County, Hungary, 8900
      • Belvárosi Egészségház
• Israel
  • Central District
    • Ẕerifin, Central District, Israel, 609300
      • Yitzhak Shamir Medical Center
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 9112001
      • Hadassah Medical Center
  • Northern District
    • Haifa, Northern District, Israel, 3109601
      • Rambam Health Care Campus
  • Tell Abīb
    • Tel Aviv, Tell Abīb, Israel, 6423906
      • Sourasky Medical Center
• Japan
  • Fukuoka, Japan, 812-0033
    • Harasanshin Hospital
  • Kyoto, Japan, 607-8062
    • Rakuwakai Otowa Hospital
  • Okayama, Japan, 701-1154
    • National Hospital Organization Okayama Medical Center
  • Osaka, Japan, 533-0024
    • Yodogawa Christian Hospital
  • Osaka, Japan, 540-0006
    • National Hospital Organization - Osaka National Hospital - Institute For Clinical Research
  • Osaka, Japan, 530-0005
    • Sakurabashi Watanabe Advanced Healthcare Hospital
  • Toyama, Japan, 930-0975
    • Toyama Prefectural Central Hospital
  • Aichi-ken
    • Kasugai, Aichi-ken, Japan, 486-8510
      • Kasugai Municipal Hospital
    • Nagoya, Aichi-ken, Japan, 466-8650
      • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Fukuoka
    • Chikushino-shi, Fukuoka, Japan, 818-8516
      • Saiseikai Futsukaichi Hospital
    • Itoshima, Fukuoka, Japan, 819-1104
      • Nakamura Cardiovascular Clinic
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Gunma University Hospital
    • Takasaki, Gunma, Japan, 370-0829
      • National Hospital Organization Takasaki General Medical Centar
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center
    • Yokohama, Kanagawa, Japan, 236-0037
      • Yokohama Minami Kyosai Hospital
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center
  • Tokyo
    • Hachiōji, Tokyo, Japan, 192-0918
      • Minamino Cardiovascular Hospital
    • Ōme, Tokyo, Japan, 198-0042
      • Ome Medical Center
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506
      • Yamanashi Prefectural Central Hospital
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-231
      • NZOZ Centrum Medyczne KERmed
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-605
      • Intercor
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-082
      • Private Practice - Dr. Ewa Mirek Bryniarska
    • Oświęcim, Lesser Poland Voivodeship, Poland, 32-660
      • MEDICOME Centrum Badań Klinicznych Oświęcimskie
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-044
      • CenterMed Lublin NZOZ
    • Lublin, Lublin Voivodeship, Poland, 20-043
      • 1 Wojskowy Szpital Kliniczny w Lublinie
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 01-249
      • Balsam Medica
  • Podkarpackie Voivodeship
    • Przemyśl, Podkarpackie Voivodeship, Poland, 37-700
      • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-704
      • KLIMED Marek Klimkiewicz
    • Bialystok, Podlaskie Voivodeship, Poland, 15-540
      • Uniwersytecki Szpital Kliniczny w Białymstoku
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 93-513
      • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
    • Lodz, Łódź Voivodeship, Poland, 90-549
      • SPZOZ Uniwersytecki Szpital Kliniczny Im. Wojskowej Akademii Medycznej UM W Łodzi Centralny Szpital Wetera -T
    • Piotrkow Trybunalski, Łódź Voivodeship, Poland, 97-300
      • IRMED Osrodek Badan Klinicznych
    • Piotrkow Trybunalski, Łódź Voivodeship, Poland, 97-300
      • Provita Profamilia
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • A Coruña [La Coruña]
    • Santiago de Compostela, A Coruña [La Coruña], Spain, 15706
      • CHUS - Hospital Clinico Universitario
  • Alicante
    • Denia, Alicante, Spain, 03700
      • Hospital de Denia Marina Salud
  • Andalusia
    • Córdoba, Andalusia, Spain, 14004
      • Hospital Universitario Reina Sofía
    • Seville, Andalusia, Spain, 41014
      • Hospital Universitario Virgen de Valme
  • Barcelona [Barcelona]
    • Badalona, Barcelona [Barcelona], Spain, 08916
      • Hospital Germans Trias I Pujol
  • Catalunya [Cataluña]
    • L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain, 08907
      • Hospital Universitari de Bellvitge
  • Jaén
    • Úbeda, Jaén, Spain, 23400
      • Hospital San Juan de la Cruz
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28034
      • Hospital Universitario Ramon y Cajal
  • Murcia, Región de
    • El Palmar, Murcia, Murcia, Región de, Spain, 30120
      • Hospital Clinico Universitario Virgen de La Arrixaca
  • Málaga
    • Málaga, Málaga, Spain, 29010
      • Hospital Universitario Virgen de la Victoria
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46010
      • Hospital Clinico de Valencia
• Turkey (Türkiye)
  • Afyonkarahisar, Turkey (Türkiye), 03030
    • Afyon Kocatepe Üniversitesi Tıp Fakültesi
  • Ankara, Turkey (Türkiye), 06170
    • Ankara Etlik City Hospital
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty Hospital
  • Izmir, Turkey (Türkiye), 35120
    • T.C. Sağlık Bakanlığı İzmir Tepecik Eğitim ve Araştırma Hast
  • Izmir, Turkey (Türkiye), 35330
    • Dokuz Eylul Universitesi Hastanesi
  • Mersin, Turkey (Türkiye), 33343
    • Mersin University
  • Bursa
    • Yıldırım, Bursa, Turkey (Türkiye), 16310
      • Bursa Yüksek İhtisas Eğitim Ve Araştırma Hastanesi
  • Eskişehir
    • Eskişehir, Eskişehir, Turkey (Türkiye), 26480
      • Eskisehir Osmangazi University
  • Kocaeli
    • İzmit, Kocaeli, Turkey (Türkiye), 41380
      • Kocaeli Üniversitesi
  • İzmir
    • Bornova, İzmir, Turkey (Türkiye), 35100
      • Ege Universitesi Hastanesi
• United Kingdom
  • Isleworth, United Kingdom, TW7 6AF
    • West Middlesex University Hospital
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital NHS Foundation Trust
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital
  • Reading, United Kingdom, RG1 5AN
    • Royal Berkshire Hospital
  • Buckinghamshire
    • High Wycombe, Buckinghamshire, United Kingdom, HP11 2TT
      • Wycombe General Hospital
  • Highland
    • Inverness, Highland, United Kingdom, IV2 3JH
      • Raigmore Hospital
  • London, City of
    • Harrow, London, City of, United Kingdom, HA1 3UJ
      • Northwick Park Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G31 2ER
      • Glasgow Royal Infirmary
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Pima Heart
  • California
    • Covina, California, United States, 91723
      • Valley Clinical Trials, Inc.
    • Northridge, California, United States, 91325
      • Valley Clinical Trials, Inc.
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Pasadena, California, United States, 91105
      • Pasadena Clinical Research
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research, Coastal Heart Medical Group
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials
    • Miami, Florida, United States, 33133
      • Infinite Clinical Research
    • Pembroke Pines, Florida, United States, 33028
      • South Florida Research Solutions - North Flamingo Road
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester, Minnesota
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
  • Texas
    • Amarillo, Texas, United States, 79109
      • PharmaTex Research
    • Dallas, Texas, United States, 75390
      • UT southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Health-Advanced Heart and Lung Disease
    • Galveston, Texas, United States, 77555-0553
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77094
      • West Houston Area Clinical Trial Consultants
    • McKinney, Texas, United States, 75071
      • Texas Institute of Cardiology, PA
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 25 mg LY3540378; Participants received 25 mg LY3540378 administered once weekly as subcutaneous (SC) injection for 26 weeks.	Drug: LY3540378; Administered SC
Experimental: 50 mg LY3540378; Participants received 50 mg LY3540378 administered once weekly as SC injection for 26 weeks.	Drug: LY3540378; Administered SC
Experimental: 100 mg LY3540378; Participants received 100 mg LY3540378 administered once weekly as SC injection for 26 weeks.	Drug: LY3540378; Administered SC
Placebo Comparator: Placebo; Participants received placebo administered once weekly as SC injection for 26 weeks.	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Left Atrial Reservoir Strain (LARS) at Week 26	Results are estimated using least squares (LS) mean from the mixed model repeated measures (MMRM) model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Left Atrial Reservoir Strain (LARS) at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 12
Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 12
Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) at Week 26	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26
Change From Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 12
Change From Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) at Week 26	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26
Change From Baseline Left Atrial End-Systolic Volume Index (LAESVI) at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 12
Change From Baseline Left Atrial End-Systolic Volume Index (LAESVI) at Week 26	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment. The unit of measure for this outcome is millilitres per minute per 1.73 square metres (mL/min/1.73 m²)	Baseline, Week 12
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26
Change From Baseline in Log-transformed Serum Creatinine at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 12
Change From Baseline in Log-transformed Serum Creatinine at Week 26	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26
Change From Baseline in Log-transformed Cystatin-C at Week 12	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 12
Change From Baseline in Log-transformed Cystatin-C at Week 26	Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment*Time + Baseline*Treatment.	Baseline, Week 26

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Publications and helpful links

General Publications

• 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 Nov;31(11):3853-3861. doi: 10.1038/s41591-025-03939-6. Epub 2025 Aug 31.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2023
• Primary Completion (Actual): January 22, 2025
• Study Completion (Actual): January 22, 2025

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 24, 2022

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 18, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 18473; J3E-MC-EZDB (Other Identifier: Eli Lilly and Company); 2023-505902-40-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No