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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 731
- 试验地点
- 143
- 主要终点
- Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Tirzepatide
Tirzepatide administered subcutaneously (SC)
干预措施: Tirzepatide (Drug)
Placebo
Placebo administered SC
干预措施: Placebo (Other)
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).
干预措施: Tirzepatide (Drug)
Placebo
Participants received placebo administered SC QW.
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
时间窗: 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
时间窗: 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.
次要结局
- Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)(Baseline, Week 52)
- Number of Participants With Time to All-Cause Death(Baseline Up To 160 Weeks)
- Win Percentage of the Hierarchical Composite Endpoint(Baseline Up To 160 Weeks)
- Percentage of Participants With New York Heart Association (NYHA) Class Change(Week 52)
- Number of HF Events and All-Cause Death(Baseline Up To 160 Weeks.)
- Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)(Baseline, Week 52)
- Percent Change From Baseline in Body Weight(Baseline, Week 52)
- Number of Participants With Time to First Occurrence of HF Events(Baseline Up To 160 Weeks)
- Number of Recurrent HF Events(Baseline Up To 160 Weeks.)