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

Open to people ages 18 years and up

• 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.

• 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.