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

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ClinicalTrials.gov Identifier: NCT05592275
Recruitment Status : Recruiting
First Posted : October 24, 2022
Last Update Posted : April 11, 2024
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Heart Failure Heart Failure With Preserved Ejection Fraction Drug: LY3540378 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 432 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 3, 2023
Estimated Primary Completion Date : November 2025
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: LY3540378 Dose 1
Participants will receive LY3540378 subcutaneously (SC).
Drug: LY3540378
Administered SC

Experimental: LY3540378 Dose 2
Participants will receive LY3540378 SC.
Drug: LY3540378
Administered SC

Experimental: LY3540378 Dose 3
Participants will receive LY3540378 SC.
Drug: LY3540378
Administered SC

Placebo Comparator: Placebo
Participants will be given placebo SC.
Drug: Placebo
Administered SC




Primary Outcome Measures :
  1. Change from Baseline in Left Atrial Reservoir Strain (LARS) [ Time Frame: Baseline, Week 26 ]

Secondary Outcome Measures :
  1. Change from Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline, Week 26 ]
  2. Change from Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) [ Time Frame: Baseline, Week 26 ]
  3. Change from Baseline Left Atrial End-Systolic Volume Index (LAESVI) [ Time Frame: Baseline, Week 26 ]
  4. Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline, Week 26 ]
    eGFR calculated by creatinine and cystatin C

  5. Change from Baseline in Serum Creatinine [ Time Frame: Baseline, Week 26 ]
  6. Change from Baseline in cystatin-C [ Time Frame: Baseline, Week 26 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05592275


Contacts
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Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com

Locations
Show Show 125 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT05592275    
Other Study ID Numbers: 18473
J3E-MC-EZDB ( Other Identifier: Eli Lilly and Company )
2023-505902-40-00 ( Other Identifier: EU Trial Number )
First Posted: October 24, 2022    Key Record Dates
Last Update Posted: April 11, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases