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

JRCT ID: jRCT2051220131

Registered date:13/12/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Heart Failure , Heart Failure With Preserved Ejection Fraction
• Date of first enrollment: 25/07/2023
• Target sample size: 432
• Countries of recruitment: Argentina,Japan,Brazil,Japan,Canada,Japan,Hungary,Japan,Poland,Japan,Spain,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

-Drug: LY3540378
Administered SC
-Drug: Placebo
Administered SC

Study Arms
-Experimental: LY3540378 Dose 1
Participants will receive LY3540378 subcutaneously (SC).
Intervention: Drug: LY3540378
-Experimental: LY3540378 Dose 2
Participants will receive LY3540378 SC.
Intervention: Drug: LY3540378
-Experimental: LY3540378 Dose 3
Participants will receive LY3540378 SC.
Intervention: Drug: LY3540378
-Placebo Comparator: Placebo
Participants will be given placebo SC.
Intervention: Drug: Placebo

Outcome(s)

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Prior chronic treatment, or prescription, with a loop diuretic (for example, furosemide, torsemide, bumetanide) for >=30 days prior to the index event. Index event is defined as a recent hospitalization for HF requiring at least 2 doses of intravenous diuretics or an out- of- hospital encounter (for example, Emergency Room, clinic visit, infusion clinic, etc.) for HF requiring at least 2 doses of intravenous diuretics.
-Chronic HF diagnosed for at least 3 months before V1 (screening).
-Documented LVEF of >=50% within 6 months prior to screening; as measured by echocardiography, radionuclide ventriculography, invasive angiography, magnetic resonance imaging (MRI), or computerized tomograph (CT).
-Had evidence of clinical HF syndrome consisting of
-Hospitalization for HF within the past 2 weeks from randomization, 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.

Exclude 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) as defined by chronic oxygen dependence. Night-time oxygen is not exclusionary.
-Uncorrected thyroid disease.

Related Information

• Primary Sponsor: Masaki Takeshi
• Secondary ID(s): NCT05592275