Heart Failure, Heart Failure With Preserved Ejection Fraction
Conditions
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
Interventions
DRUGLY3540378
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Atrial Reservoir Strain (LARS) at Week 26 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Atrial Reservoir Strain (LARS) at Week 12 | 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. |
| Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) at Week 12 | 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. |
| Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) at Week 26 | 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. |
| Change From Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) at Week 12 | 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. |
| Change From Baseline in Left Atrial End-Diastolic Volume Index (LAEDVI) at Week 26 | 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. |
| Change From Baseline Left Atrial End-Systolic Volume Index (LAESVI) at Week 26 | 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. |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 | 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) |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26 | 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. |
| Change From Baseline in Log-transformed Serum Creatinine at Week 12 | 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. |
| Change From Baseline in Log-transformed Serum Creatinine at Week 26 | 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. |
| Change From Baseline in Log-transformed Cystatin-C at Week 12 | 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. |
| Change From Baseline Left Atrial End-Systolic Volume Index (LAESVI) at Week 12 | 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. |
| Change From Baseline in Log-transformed Cystatin-C at Week 26 | 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. |
Countries
Argentina, Brazil, Canada, Czechia, Hungary, Israel, Japan, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORCall 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
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 74.70 years STANDARD_DEVIATION 8.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 293 Participants |
| Region of Enrollment Argentina | 23 participants |
| Region of Enrollment Brazil | 62 participants |
| Region of Enrollment Canada | 3 participants |
| Region of Enrollment Hungary | 11 participants |
| Region of Enrollment Israel | 4 participants |
| Region of Enrollment Japan | 7 participants |
| Region of Enrollment Poland | 14 participants |
| Region of Enrollment Spain | 14 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 79 | 2 / 83 | 3 / 81 | 2 / 88 |
| other Total, other adverse events | 50 / 79 | 57 / 83 | 46 / 81 | 55 / 88 |
| serious Total, serious adverse events | 19 / 79 | 26 / 83 | 20 / 81 | 15 / 88 |
Outcome results
None listed