A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction and Obesity

Study Overview
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Brief Summary
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The main purpose of this study is to assess the efficacy and safety of Tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity.

Detailed Description
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The study will continue until approximately 52 weeks after the last participant is randomized. The maximum duration of an individual's participation is estimated to be 120 weeks and will depend on duration of study enrollment.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Heart Failure With Preserved Ejection Fraction and Obesity (SUMMIT)

Conditions
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Obesity, Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Drug: Tirzepatide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of stable heart failure (NYHA class II-IV) and left ventricular ejection fraction (LVEF) ≥50% Elevated NT-proBNP (N-terminal pro B-type natriuretic peptide) > 200 pg/ml for participants without atrial fibrillation (AF), or >600 picogram/milliliter (pg/ml) for participants with AF, Structural heart disease (Left atrial enlargement) or Elevated left ventricular filling pressure Estimated glomerular filtration rate (eGFR) <70 milliliter (ml)/minute (min)/1.73m² at screening, or HF decompensation within 12 months of screening, Stable dose of heart failure medications within 4 weeks of screening Body mass index (BMI) ≥30 kilograms per meter squared (kg/m²) 6MWD 100-425m KCCQ CSS ≤80 Exclusion Criteria: Have had a major cardiovascular event within the last 90 days of screening Have had acute decompensated heart failure within 4 weeks of screening Have non cardiac causes of functional impairment such as pulmonary arterial hypertension (PAH), severe chronic obstructive pulmonary disease (COPD), anemia, thyroid disease, musculoskeletal disease or orthopedic conditions Presence of cardiac amyloidosis, cardiac accumulation disease, cardiomyopathy and severe valvular hear disease HbA1c ≥9.5% or uncontrolled diabetes History of proliferative diabetic retinopathy or diabetic maculopathy Have a history of pancreatitis eGFR <15 mL/min/1.73 m² or requiring dialysis at screening

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide<br>Tirzepatide administered subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Placebo administered SC | Other: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Hierarchical Composite of All-Cause Mortality, Heart Failure Events, 6-minute Walk Test Distance (6MWD) and Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) Category | Hierarchical Composite of Time to All-Cause Mortality, Number of Heart Failure Events, Time to First HF Events, 6MWD, and KCCQ CSS will be assessed by the win ratio. The reported unit will be the total wins for each treatment group from performing a hierarchical comparison of the components. | Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) | 
| Change from Baseline in Exercise Capacity as Measured by 6MWD |  | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Body Weight Loss |  | Baseline, Week 52 | 
| Change from Baseline in the KCCQ CSS |  | Baseline, Week 52 | 
| Change from Baseline in 6MWD |  | Baseline, Week 24 | 
| Percentage of Participants with New York Heart Association (NYHA) Class Change |  | Week 52 | 
| Time to First Occurrence of HF Events or Cardiovascular (CV) Death |  | Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) | 
| Time to First Occurrence of HF Events or All-Cause Death |  | Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) | 
| Time to First Occurrence of HF Events |  | Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) | 
| Time to Recurrent Events of HF Events and CV Death |  | Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) | 
| Time to Recurrent Events of HF Events |  | Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure with Preserved Ejection Fraction (HFpEF)