Clinical trial NCT05592275: A Study of LY3540378 in Participants With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Failure
Heart Failure With Preserved Ejection Fraction
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-10-24
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Left Atrial Reservoir Strain (LARS)
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change from Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline, Week 26
measure: Change from Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI)
timeFrame: Baseline, Week 26
measure: Change from Baseline Left Atrial End-Systolic Volume Index (LAESVI)
timeFrame: Baseline, Week 26
measure: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline, Week 26
measure: Change from Baseline in Serum Creatinine
timeFrame: Baseline, Week 26
measure: Change from Baseline in cystatin-C
timeFrame: Baseline, Week 26
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Pima Heart
state: Arizona
city: Covina
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Pasadena
country: United States
facility: Pasadena Clinical Research
state: California
city: Santa Ana
country: United States
facility: Velocity Clinical Research, Coastal Heart Medical Group
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Miami
country: United States
facility: Infinite Clinical Research
state: Florida
city: Pembroke Pines
country: United States
facility: South Florida Research Solutions - North Flamingo Road
state: Florida
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina Medical Center
state: North Carolina
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Amarillo
country: United States
facility: PharmaTex Research
state: Texas
city: Dallas
country: United States
facility: Baylor Scott & White Health-Advanced Heart and Lung Disease
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: West Houston Area Clinical Trial Consultants
state: Texas
city: McKinney
country: United States
facility: Texas Institute of Cardiology, PA
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
state: Buenos Aires
city: Zárate
country: Argentina
facility: Instituto de Investigaciones Clinicas Zarate
state: Buenos Aires
city: Balvanera
country: Argentina
facility: Investigaciones Medicas Imoba Srl
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Sanatorio Anchorena Recoleta
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Mautalen Salud e Investigación
state: Ciudad Autónoma De Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
state: Ciudad Autónoma De Buenos Aires
city: Río Cuarto
country: Argentina
facility: Instituto Médico Río Cuarto
state: Córdoba
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto de Investigaciones Clinicas Rosario
state: Santa Fe
city: Venado Tuerto
country: Argentina
facility: Sanatorio San Martin
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones Clínicas Tucumán
state: Tucumán
city: Buenos Aires
country: Argentina
facility: CEMEDIC
city: Buenos Aires
country: Argentina
facility: Fundación Respirar
city: Santa Fe
country: Argentina
facility: Centro de Investigaciones Clinicas del Litoral
city: Santa Fe
country: Argentina
facility: Clínica de Nefrología, Urología y Enfermedades Cardiovasculares
city: Rio Branco
country: Brazil
facility: Centro de Pesquisa Silvestre Santé
state: Acre
city: Goiania
country: Brazil
facility: Universidade Federal de Goias
state: Goiás
city: Curitiba
country: Brazil
facility: PUC Trials- Nucleo de Pesquisa clinica da Escola de Medicina da PUCPR
state: Paraná
city: Acaraju
country: Brazil
facility: Centro de Pesquisa Clinica do Coracao
state: Sergipe
city: Campinas
country: Brazil
facility: Centro de Pesquisa Sao Lucas
state: São Paulo
city: Campinas
country: Brazil
facility: Instituto de Pesquisa clinica de Campinas
state: São Paulo
city: Marilia
country: Brazil
facility: Instituto Do Coracao De Marilia
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: CAPED Centro Avancado Pesquisa e Diagnostica
state: São Paulo
city: Santo André
country: Brazil
facility: Pesquisare Saude
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Santa Paula
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Incor - Instituto do Coracao
state: São Paulo
city: Tatui
country: Brazil
facility: Instituto de Molestias Cardiovasculares de Tatui
state: São Paulo
city: Votuporanga
country: Brazil
facility: Integral Pesquisa e Ensino
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Hospital São Lucas de Copacabana
city: Rio de Janeiro
country: Brazil
facility: Instituto D'Or Pesquisa e Ensino
city: Surrey
country: Canada
facility: SMH Cardiology Clinical Trials
state: British Columbia
city: Cambridge
country: Canada
facility: Private Practice - Dr. Saul Vizel
state: Ontario
city: Newmarket
country: Canada
facility: PACE Cardiology
state: Ontario
city: North York
country: Canada
facility: North York Diagnostic and Cardiac Centre
state: Ontario
city: Oakville
country: Canada
facility: Oakville Trafalgar Memorial Hospital
state: Ontario
city: Scarborough
country: Canada
facility: Heart Health Institute - Scarborough Office
state: Ontario
city: Toronto
country: Canada
facility: Medicus MFC Research Clinic
state: Ontario
city: Waterloo
country: Canada
facility: CPS Research
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universite de Sherbrooke - Hôtel-Dieu Hospital
state: Quebec
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Bohunice
state: Brno-město
city: Brno
country: Czechia
facility: Fakultni Nemocnice u sv. Anny v Brne
state: Jihomoravský Kraj
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
state: Csongrád
city: Nyiregyhaza
country: Hungary
facility: Medifarma 98 Kft
state: Nyíregyháza
city: Kistarcsa
country: Hungary
facility: Kistarcsai Flor Ferenc Korhaz
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Belvárosi Egészségház
state: Zala
city: Budapest
country: Hungary
facility: Dél-Pesti Centrumkórház
city: Budapest
country: Hungary
facility: Semmelweis University
city: Zerifin
country: Israel
facility: Yitzhak Shamir Medical Center
state: HaMerkaz
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: HaTsafon
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
state: Tell Abīb
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Kasugai
country: Japan
facility: Kasugai Municipal Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Chikushino
country: Japan
facility: Saiseikai Futsukaichi Hospital
state: Fukuoka
city: Itoshima
country: Japan
facility: Nakamura Cardiovascular Clinic
state: Fukuoka
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Takasaki
country: Japan
facility: National Hospital Organization Takasaki General Medical Centar
state: Gunma
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama Minami Kyosai Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
state: Kanagawa
city: Hachioji
country: Japan
facility: Minamino Cardiovascular Hospital
state: Tokyo
city: Ome
country: Japan
facility: Ome Medical Center
state: Tokyo
city: Kofu
country: Japan
facility: Yamanashi Prefectural Central Hospital
state: Yamanashi
city: Fukuoka
country: Japan
facility: Harasanshin Hospital
city: Kyoto
country: Japan
facility: Rakuwakai Otowa Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Sakurabashi Watanabe Advanced Healthcare Hospital
city: Osaka
country: Japan
facility: Yodogawa Christian Hospital
city: Osaka
country: Japan
facility: National Hospital Organization - Osaka National Hospital - Institute For Clinical Research
city: Toyama
country: Japan
facility: Toyama Prefectural Central Hospital
city: Bydgoszcz
country: Poland
facility: NZOZ Centrum Medyczne KERmed
state: Kujawsko-pomorskie
city: Bydgoszcz
country: Poland
facility: INTERCOR
state: Kujawsko-pomorskie
city: Lublin
country: Poland
facility: 1 Wojskowy Szpital Kliniczny w Lublinie
state: Lubelskie
city: Lublin
country: Poland
facility: CenterMed Lublin NZOZ
state: Lubelskie
city: Warsaw
country: Poland
facility: Balsam Medica
state: Mazowieckie
city: Krakow
country: Poland
facility: Private Practice - Dr. Ewa Mirek Bryniarska
state: Małopolskie
city: Oświęcim
country: Poland
facility: MEDICOME Centrum Badań Klinicznych Oświęcimskie
state: Małopolskie
city: Przemysl
country: Poland
facility: Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu
state: Podkarpackie
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Białymstoku
state: Podlaskie
city: Białystok
country: Poland
facility: KLIMED Marek Klimkiewicz
state: Podlaskie
city: Piotrkow Trybunalski
country: Poland
facility: IRMED Osrodek Badan Klinicznych
state: Łódzkie
city: Piotrków Trybunalski
country: Poland
facility: Provita Profamilia
state: Łódzkie
city: Łódź
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny Im. Wojskowej Akademii Medycznej UM W Łodzi Centralny Szpital Wetera -T
state: Łódzkie
city: Łódź
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
state: Łódzkie
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
state: A Coruña [La Coruña]
city: Dénia
country: Spain
facility: Hospital de Denia Marina Salud
state: Alicante
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Andalucía
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
state: Andalucía
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona [Barcelona]
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Catalunya [Cataluña]
city: Ubeda
country: Spain
facility: Hospital San Juan de la Cruz
state: Jaén
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad De
city: El Palmar, Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia, Región De
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Málaga
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
state: Valenciana, Comunitat
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Yıldırım
country: Turkey
facility: Bursa Yüksek İhtisas Eğitim Ve Araştırma Hastanesi
state: Bursa
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi University
state: Eskişehir
city: Bornova
country: Turkey
facility: Ege Universitesi Hastanesi
state: İzmir
city: Izmit
country: Turkey
facility: Kocaeli Üniversitesi
state: Kocaeli
city: Afyonkarahisar
country: Turkey
facility: Afyon Kocatepe Üniversitesi Tıp Fakültesi
city: Ankara
country: Turkey
facility: Ankara Etlik City Hospital
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty Hospital
city: Izmir
country: Turkey
facility: T.C. Sağlık Bakanlığı İzmir Tepecik Eğitim ve Araştırma Hast
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Hastanesi
city: Mersin
country: Turkey
facility: Mersin University
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: Buckinghamshire
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Highland
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: London, City Of
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
state: Scotland
city: Isleworth
country: United Kingdom
facility: West Middlesex University Hospital
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
Study officials:
affiliation: Eli Lilly and Company
name: 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
References: