Semaglutide for Reducing Cardiovascular Events in Patients Undergoing Transcatether Aortic Valve Replacement
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 826
- 主要终点
- CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF
研究概览
简要总结
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial evaluating the safety and efficacy of once-weekly semaglutide 2.4 mg in adult patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) who meet current clinical criteria for semaglutide treatment. A total of 826 participants will be randomized 1:1 to receive semaglutide or placebo as an add-on to standard-of-care, starting 3 months before TAVR and continuing for 24 months post-procedure. The primary endpoint is time to first occurrence of a composite of cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke or transient ischemic accident (TIA), and hospitalization for heart failure (HF). The study is event-driven and powered to detect a 20% relative risk reduction in primary outcome events. This trial aims to address the unmet need for medical therapies that improve outcomes in patients with severe AS following TAVR, with potential for direct clinical implementation.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study. Participants, care providers, investigators, and outcome assessors will be blinded to treatment allocation. Semaglutide and placebo will be identical in appearance and administered in the same manner.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects are eligible to be included in the trial only if all of the following criteria apply:
- •Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- •Adults (≥18 years) undergoing TAVR for severe AS, and
- •BMI ≥30 kg/m2, or
- •BMI 27-30 kg/m2, AND at least one of the following:
- •Dysglycemia (prediabetes or type 2 diabetes) ≥90 days prior to the day of screening with HbA1c of ≤ 10.0% as measured at the screening visit.
- •Arterial Hypertension
- •Hypercholesterolemia
- •Obstructive sleep apnea
- •History of stroke (ischemic or hemorrhagic)
- •History of myocardial infarction
- •Symptomatic peripheral artery disease (intermittent claudication with ankle-brachial index <0.85, peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease)
排除标准
- •Treatment with an GLP-1 receptor agonist within the previous 90 days.
- •Myocardial infarction, stroke, hospitalization for unstable angina or transient ischemic attack within the previous 60 days.
- •Planned coronary, carotid or peripheral artery revascularization known on the day of screening.
- •eGFR <25 mL/min/1.73 m² or intermittent hemodialysis or peritoneal dialysis.
- •Presence of acute pancreatitis within the last 180 days prior to screening.
- •History or presence of chronic pancreatitis.
- •Self-reported change in body weight of >5 kg within 90 days before screening.
- •Bariatric surgery prior to screening or planned bariatric surgery within the trial time course.
- •Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell cancer and any carcinoma in-situ are allowed.
- •Known or suspected hypersensitivity to trial product(s) or related products.
- •Participation in any clinical trial of an approved or non-approved device for the treatment of aortic stenosis or obesity within 30 days before screening.
- •Receipt of any investigational medicinal product within 30 days before screening.
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- •Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
- •Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
研究组 & 干预措施
Control Arm
干预措施: Placebo (Drug)
Treatment Arm
干预措施: Wegovy ® (Drug)
结局指标
主要结局
CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF
时间窗: From randomization through 12 and 27 months
From randomization to first occurrence of a composite endpoint consisting of: CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF.
次要结局
- A 5-component composite nephropathy endpoint consisting of: onset of persistent macroalbuminuria, persistent 50% reduction in eGFR compared with baseline (randomization), onset of persistent eGFR < 15 ml/min/1.73m2, initiation of chronic renal replacemen(From randomization at 12 and 27 months)
- Incidence rate of each component of the primary outcome.(From randomization at 12 months and 27 months)
- Change in high sensitivity C-Reactive Protein (hsCRP) (mg/L)(From randomization at 12 and 27 months)
- Change in Lipid Profile (mg/dL)(From randomization at 12 and 27 months)
- Change in waist circumference(From randomization at 12 and 27 months)
- Change in HbA1c (%, mmol /mol)(From randomization at 12 and 27 months)
- Change in systolic blood pressure(From randomization at 12 and 27 months)
- Changes in LV remodeling (echocardiographic assessment of LV size, mass, systolic and diastolic function)(From randomization at 12 and 27 months)
- Change in loop diuretic medication(From randomization at 12 and 27 months)
- Change in H2FPEF score(From randomization at 12 and 27 months)
- Change in NT-proBNP(From randomization at 12 and 27 months)
- Change in KCCQ score(From randomization at 12 and 27 months.)
- Subject experiencing deterioration in NYHA functional class(From randomization at 12 and 27 months)
- Change in body weight (%)(From randomization at 12 and 27 months.)
研究者
Nina Ajmone Marsan
MD, PhD
Leiden University Medical Center