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

NCT05592275
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Phase
Phase 2
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Recruitment status
Terminated
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Participants
332
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Lead sponsor
Eli Lilly and Company
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Start date
2023-02-03
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Number of sites
137
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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
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Short title
A Study of LY3540378 in Participants With Worsening Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)
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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)
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Control arm
Placebo
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Terminated
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Phase
Phase 2
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Study type
Interventional
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Reason stopped
An interim was conducted and after review of available data, including efficacy evaluation of heart failure events, Lilly is terminating the study due to low likelihood of study success for this HFpEF patient population.
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Completion date
2025-01-22
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First posted
2022-10-24
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Registry last updated
2026-02-05
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Primary completion date
2025-01-22
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Start date
2023-02-03
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Actual participants
332
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Participants
332
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
137
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Eli Lilly and Company
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05592275
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ClinicalTrials.gov ID
NCT05592275
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design
clinicaltrials.gov

  1. Change From Baseline in Left Atrial Reservoir Strain (LARS) at Week 26

    Timeframe: Baseline, 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.

  1. Change From Baseline in Left Atrial Reservoir Strain (LARS) at Week 12

    Timeframe: Baseline, Week 12

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  2. Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) at Week 12

    Timeframe: Baseline, Week 12

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  3. Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) at Week 26

    Timeframe: Baseline, Week 26

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  4. Change From Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) at Week 12

    Timeframe: Baseline, Week 12

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  5. Change From Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) at Week 26

    Timeframe: Baseline, Week 26

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  6. Change From Baseline Left Atrial End-Systolic Volume Index (LAESVI) at Week 12

    Timeframe: Baseline, Week 12

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  7. Change From Baseline Left Atrial End-Systolic Volume Index (LAESVI) at Week 26

    Timeframe: Baseline, Week 26

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  8. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12

    Timeframe: Baseline, 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)

  9. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26

    Timeframe: Baseline, Week 26

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  10. Change From Baseline in Log-transformed Serum Creatinine at Week 12

    Timeframe: Baseline, Week 12

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  11. Change From Baseline in Log-transformed Serum Creatinine at Week 26

    Timeframe: Baseline, Week 26

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  12. Change From Baseline in Log-transformed Cystatin-C at Week 12

    Timeframe: Baseline, Week 12

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

  13. Change From Baseline in Log-transformed Cystatin-C at Week 26

    Timeframe: Baseline, Week 26

    Results are estimated using LS mean from the MMRM model: Change from baseline = Baseline + Strata + Gender + Treatment + Time + Treatment\*Time + Baseline\*Treatment.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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.

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Pima HeartTucson, United States
  • Valley Clinical Trials, Inc.Covina, United States
  • Valley Clinical Trials, Inc.Northridge, United States
  • University of California Irvine Medical CenterOrange, United States
  • Pasadena Clinical ResearchPasadena, United States
  • Velocity Clinical Research, Coastal Heart Medical GroupSanta Ana, United States
  • Excel Medical Clinical TrialsBoca Raton, United States
  • Infinite Clinical ResearchMiami, United States
  • South Florida Research Solutions - North Flamingo RoadPembroke Pines, United States
  • University Medical Center New OrleansNew Orleans, United States
  • Boston Medical CenterBoston, United States
  • Henry Ford HospitalDetroit, United States
  • Mayo Clinic in Rochester, MinnesotaRochester, United States
  • University of North Carolina Medical CenterChapel Hill, United States
  • Abington Memorial HospitalAbington, United States
  • PharmaTex ResearchAmarillo, United States
  • Baylor Scott & White Health-Advanced Heart and Lung DiseaseDallas, United States
  • UT Southwestern Medical CenterDallas, United States
  • University of Texas Medical BranchGalveston, United States
  • West Houston Area Clinical Trial ConsultantsHouston, United States
  • Texas Institute of Cardiology, PAMcKinney, United States
  • University of Wisconsin Hospital and ClinicsMadison, United States
  • Centro de Investigaciones Metabólicas (CINME)Ciudad Autónoma de Buenos Aires, Argentina
  • Instituto de Investigaciones Clinicas ZarateZárate, Argentina
  • Investigaciones Medicas Imoba SrlBalvanera, Argentina

And 112 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-505902-40-00
  • J3E-MC-EZDB
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)