A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial
- Conditions
- ObesityHeart Failure With Preserved Ejection Fraction (HFpEF)
- Interventions
- Other: Placebo
- Registration Number
- NCT04847557
- Lead Sponsor
- Eli Lilly and Company
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 731
- 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 picogram/milliliter (pg/ml) for participants without atrial fibrillation (AF), or >600 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 100-425 meters
- KCCQ CSS ≤80
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tirzepatide Tirzepatide Participants received a starting dose of 2.5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW) and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or maximum tolerated dose (MTD) tolerated by the participant (5 mg QW or 10 mg QW). Placebo Placebo Participants received placebo administered SC QW. Placebo Placebo Placebo administered SC Tirzepatide Tirzepatide Tirzepatide administered subcutaneously (SC)
- Primary Outcome Measures
Name Time Method Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) Baseline, Week 52 The KCCQ is a 23-item, participant self-administered questionnaire that assesses impacts of heart failure "over the past 2 weeks" on the following 7 domains:
* Physical Limitation (6)
* Symptom Stability (1)
* Symptom Frequency (4)
* Symptom Burden (3)
* Self-Efficacy (2)
* Quality of Life (3)
* Social Limitation (4)
Each of the 23 individual items are answered on Likert scales of varying lengths (5, 6, or 7-point scales).
KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are obtained by averaging the associated individual items and transforming the score to a 0 to 100 range. Higher scores indicate better health status.
Least Square (LS) mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables .First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes Baseline Up To 160 weeks Clinical Endpoint Committe confirmed Occurrences of CV outcomes were reported here. HF outcomes consisted of cardiovascular death and HF events.
The HF events were defined as worsening clinical symptoms or signs related to HF, which are meaningful to the participant and require intensification of treatment characterized by 1 or more of the following:
* hospitalization for heart failure regardless of duration or treatment received
* use of intravenous drug, usually an intravenous diuretic, but may include intravenous vasodilators or positive inotropic drugs, or
* augmentation or increase in oral diuretic therapy.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) Baseline, Week 52 Percent change from baseline in hsCRP was reported. LS Mean was determined using ANCOVA model with log (actual measurement/baseline) = log (baseline) + HF decompensation within 12 months of screening + T2DM status + baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables.
Number of Participants With Time to All-Cause Death Baseline Up To 160 Weeks All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.
Win Percentage of the Hierarchical Composite Endpoint Baseline Up To 160 Weeks Hierarchical Composite Endpoint included time to all-cause death, number of HF events, time to first HF events, KCCQ-CSS, 6MWD.
The winner was determined in each pair-wise comparison in the following order:
* A delayed first occurrence of all-cause death
* If the pair cannot be differentiated based on death, winner has fewer HF events
* If the pair cannot be differentiated by number of HF events, winner has delayed time to occurrence of first HF event
* If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in 6MWD
* If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in KCCQ-CSS
* Otherwise the pair will be recorded as tied.
Reported unit is the total percent of "wins" for each treatment group from performing such a hierarchical comparison across stratification factors in the study.Percentage of Participants With New York Heart Association (NYHA) Class Change Week 52 Percentage of participants with NYHA class change at Week 52 was reported.
Number of HF Events and All-Cause Death Baseline Up To 160 Weeks. Number of HF events and all-cause death are reported.
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD) Baseline, Week 52 Participants performed an exercise capacity assessment using the 6-Minute Walk Test (6MWT) and the distance covered (6MWD) was assessed in meters. The 6MWT was performed indoors on a straight, flat, hard surface that is at least 30 meters in length. The greater distance walked meant better physical capacity.
LS Mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables.Percent Change From Baseline in Body Weight Baseline, Week 52 Percent change in bodyweight was reported. LS mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables.
Number of Participants With Time to First Occurrence of HF Events Baseline Up To 160 Weeks Number of participants with time to first occurrence of HF events are reported.
Number of Recurrent HF Events Baseline Up To 160 Weeks. Number of recurrent HF events were reported.
Related Research Topics
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Trial Locations
- Locations (143)
Heart Center Research
🇺🇸Huntsville, Alabama, United States
Westside Medical Associates of Los Angeles
🇺🇸Beverly Hills, California, United States
Valley Clinical Trials, Inc.
🇺🇸Northridge, California, United States
Amicis Research Center
🇺🇸Granada Hills, California, United States
University of California San Diego - La Jolla
🇺🇸La Jolla, California, United States
The Lundquist Institute
🇺🇸Torrance, California, United States
South Denver Cardiology Associates
🇺🇸Littleton, Colorado, United States
Cardiology Associates of Fairfield County, P.C.
🇺🇸Stamford, Connecticut, United States
Excel Medical Clinical Trials
🇺🇸Boca Raton, Florida, United States
Clearwater Cardiovascular & Interventional Consultants M.D., P.A.
🇺🇸Safety Harbor, Florida, United States
Scroll for more (133 remaining)Heart Center Research🇺🇸Huntsville, Alabama, United States