A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial

• ClinicalTrials.gov Identifier: NCT04847557
• Recruitment Status: Active, not recruiting
• First Posted: April 19, 2021
• Last Update Posted: April 22, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: February 26, 2021
• First Posted Date: April 19, 2021
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: April 20, 2021
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2024)

• Change from Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) [ Time Frame: Baseline, Week 52 ]
• Occurrence of the Composite Endpoint of Cardiovascular (CV) Death and/or Heart Failure (HF) Events Over Time [ Time Frame: Baseline to Study Completion (estimated up to 120 weeks) ]

Original Primary Outcome Measures (submitted: April 13, 2021)

• 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 [ Time Frame: Randomization (Week 0) to Study Completion (Estimated Up to 120 Weeks) ]
  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.
• Change from Baseline in Exercise Capacity as Measured by 6MWD [ Time Frame: Baseline, Week 52 ]

Current Secondary Outcome Measures (submitted: April 18, 2024)

• Change from Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD) [ Time Frame: Baseline, Week 52 ]
• Percent Change from Baseline in Body Weight [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP) [ Time Frame: Baseline, Week 52 ]
• A hierarchical Composite of All-Cause Mortality, HF events, KCCQ-CSS, and 6MWD Category [ Time Frame: Baseline to Study Completion (estimated up to 120 weeks) ]
  Hierarchical Composite of Time to All-Cause Mortality, Number of Heart Failure Events, Time to First HF Events, KCCQ-CSS, and 6MWD 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.
• Percentage of Participants with New York Heart Association (NYHA) Class Change [ Time Frame: Week 52 ]
• Time to All-Cause Death [ Time Frame: Baseline to Study Completion (estimated up to 120 weeks) ]
• Time to First Occurrence of HF Events [ Time Frame: Baseline to Study Completion (estimated up to 120 weeks) ]
• Time to Recurrent HF Events and All-Cause Death [ Time Frame: Baseline to Study Completion (estimated up to 120 weeks) ]
• Time to Recurrent HF Events [ Time Frame: Baseline to Study Completion (estimated up to 120 weeks) ]

Original Secondary Outcome Measures (submitted: April 13, 2021)

• Percent Change from Baseline in Body Weight Loss [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in the KCCQ CSS [ Time Frame: Baseline, Week 52 ]
• Change from Baseline in 6MWD [ Time Frame: Baseline, Week 24 ]
• Percentage of Participants with New York Heart Association (NYHA) Class Change [ Time Frame: Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial
• Official Title: 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)
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Obesity
• Heart Failure With Preserved Ejection Fraction (HFpEF)

Intervention

• Drug: Tirzepatide
  Administered SC
  Other Name: LY3298176
• Other: Placebo
  Administered SC

Study Arms

• Experimental: Tirzepatide
  Tirzepatide administered subcutaneously (SC)
  Intervention: Drug: Tirzepatide
• Placebo Comparator: Placebo
  Placebo administered SC
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 18, 2024): 731
• Original Estimated Enrollment (submitted: April 13, 2021): 700
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 heart 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, China, India, Israel, Mexico, Puerto Rico, Russian Federation, Taiwan, United States

Administrative Information

• NCT Number: NCT04847557
• Other Study ID Numbers: 17757; I8F-MC-GPID ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 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

• PRS Account: Eli Lilly and Company
• Verification Date: April 2024