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

• Status: Not yet recruiting
• Trial end date: 2024-09-06
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company

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. 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.

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) as defined by chronic oxygen dependence. Night-time oxygen is not exclusionary.

• Uncorrected thyroid disease.