NCT05371496已完成4 期
Evaluation of the Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction (CAMEO-SEMA)
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Pulmonary Capillary Wedge Pressure (PCWP)
研究概览
简要总结
The purpose of this research is to find out if an aggressive intervention to lose weight, will improve symptoms in patients with obesity-related cardiomyopathy, which is also known as the obese phenotype of heart failure with preserved ejection fraction (HFpEF).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI ≥ 30.0 kg/m
- •NYHA Class II-IV.
- •LVEF ≥ 50 % within the preceding year.
- •No hospitalizations due to heart failure in the preceding 30 days.
- •At least one of the following:
- •Mean PCWP ≥ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≥ 15 mmHg documented during catheterization at rest, or PCWP or LVEDP ≥ 25 mmHg documented during catheterization at exercise.
- •If BMI < 35.0: NT-proBNP ≥ 220 pg/mL (for patients with sinus rhythm) or NT-proBNP ≥ 660 pg/mL (for patients with persistent/permanent atrial fibrillation); if BMI ≥ 35.0: NT-proBNP ≥ 125 pg/mL (for patients in sinus rhythm) or NT-proBNP ≥ 375 pg/mL (for patients with persistent/ permanent atrial fibrillation) at screening (NT-proBNP analyzed by the central laboratory) in combination with at least one of the following (documented by echocardiography within 12 months prior to or at screening): i. Septal é < 7 cm/sec or lateral é < 10 cm/sec or average E/é ≥
- •ii. PA systolic pressure > 35 mmHg. iii. Left atrial (LA) enlargement (LA width ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20.0 cm2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m2). iv. LV hypertrophy with septal thickness or posterior wall thickness ≥ 1.2 cm
- •Hospitalization with a primary diagnosis of decompensated heart failure which required intravenous (IV) loop diuretic treatment, within the previous 12 months in combination with at least two of the following (documented by echocardiography within 12 months prior to or at screening): i. Septal é < 7 cm/sec or lateral é < 10 cm/sec or average E/é ≥
- •ii. PA systolic pressure > 35 mmHg. iii. LA enlargement (LA width ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20.0 cm2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m2). iv. LV hypertrophy with septal thickness or posterior wall thickness ≥ 1.2 cm. v. Ongoing use of diuretic therapy for at least 30 days prior to screening.
排除标准
- •Cardiovascular-related:
- •Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
- •Systolic blood pressure > 160 mmHg at screening.
- •Planned coronary, carotid or peripheral artery revascularization.
- •Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, primary pulmonary arterial hypertension, chronic obstructive pulmonary disease, right heart failure due to pulmonary disease, complex congenital heart disease, anemia, or more than moderate mitral or aortic heart valve disease).
- •Amyloid cardiomyopathy may be present in 5-15% of patients presenting with the clinical syndrome of HFpEF,60-62 and patients with amyloid may respond differently to WL intervention. To enhance the scientific rigor of the trial by ensuring a homogenous population of true primary HFpEF, we will carefully evaluate for the presence of amyloid using the approach outlined in a recent scientific statement from the AHA,63 which is also consistent with our current clinical practice.
- •Specifically, potential participants will be evaluated for clues or risk factors for underlying cardiac amyloid including intolerance to antihypertensives, hypotension, orthostatic intolerance, persistent low-grade elevation in troponin, low QRS voltage on ECG, unexplained AV block or prior pacemaker, unexplained LV or RV wall thickening, impaired LV global longitudinal strain with apical sparing by echocardiography, family history of cardiomyopathy, neuropathy, autonomic dysfunction, carpal tunnel syndrome, lumbar spinal stenosis, family history of polyneuropathy, or black race. Patients with these risk factors will undergo screening evaluation for amyloid prior to consent in CAMEO-SEMA as part of best clinical practice. This includes screening for monoclonal light chain as first step, followed by hematology consultation if the screen is positive. Patients with risk factors but no monoclonal light chain will then undergo Tc-99m-PYP scan to rule out cardiac amyloid.
- •Obesity-related:
- •Bariatric surgery prior to screening within 5 years of screening or planned bariatric surgery within the trial time course.
- •A self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening irrespective of medical records.
- •Glycemia-related:
- •HbA1c ≥ 10.0% based on latest available value from medical records, not older than 3 months
- •History of type 1 diabetes (history of gestational diabetes is allowed).
- •Treatment with any GLP-1 receptor agonist within 90 days prior to the day of screening.
- •General health and safety:
- •Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- •Presence of acute pancreatitis within the last 180 days prior to screening.
- •History or presence of chronic pancreatitis.
- •End-stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis.
- •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 heart failure 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
Placebo Treatment
Placebo Comparator
Subjects will receive matching placebo once weekly in addition to counselling on healthy lifestyle intervention
干预措施: Counselling on healthy lifestyle intervention (Behavioral)
Semaglutide Treatment
Active Comparator
Subjects will receive Semaglutide once weekly in addition to counselling on healthy lifestyle intervention
干预措施: Semaglutide (Drug)
Semaglutide Treatment
Active Comparator
Subjects will receive Semaglutide once weekly in addition to counselling on healthy lifestyle intervention
干预措施: Counselling on healthy lifestyle intervention (Behavioral)
Placebo Treatment
Placebo Comparator
Subjects will receive matching placebo once weekly in addition to counselling on healthy lifestyle intervention
干预措施: Placebo (Drug)
结局指标
主要结局
Pulmonary Capillary Wedge Pressure (PCWP)
时间窗: Baseline, 12 months
Change in PCWP during exercise, reported in mmHG
次要结局
- Trans-cardiac uptake of free fatty acids (FFA) at rest(Baseline, 12 months)
- Trans-cardiac uptake of free fatty acids (FFA) during exercise(Baseline, 12 months)
- Trans-cardiac uptake of glucose at rest(Baseline, 12 months)
- Trans-cardiac uptake of glucose during exercise(Baseline, 12 months)
- Trans-cardiac uptake of ketone bodies at rest(Baseline, 12 months)
- Trans-cardiac uptake of ketone bodies during exercise(Baseline, 12 months)
- Left ventricular (LV) global longitudinal strain(Baseline, 12 months)
- Left Atrial (LA) reservoir strain(Baseline, 12 months)
- Right Ventricular (RV) free wall strain(Baseline, 12 months)
- Myocardial mass(Baseline, 12 months)
- Myocardial volume(Baseline, 12 months)
- Myocardial fat content(Baseline, 12 months)
- Body fat mass(Baseline, 12 months)
- Visceral fat content(Baseline, 12 months)
- Total blood volume(Baseline, 12 months)
- Total plasma volume(Baseline, 12 months)
- Change in Quality of Life (QOL) as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)(Baseline, 12 months)
- Change in skeletal muscle mass(Baseline, 12 months)
- Change in cardiac chamber mass(Baseline, 12 months)
- Proportion of patients that no longer fulfill hemodynamic criteria for HFpEF at end of trial(12 months)
- Change in peak volume of oxygen(Baseline, 12 months)
- Change in markers of insulin sensitivity(Baseline, 12 months)
- Change in adipocyte cell size(Baseline, 12 months)
- Change in pulmonary arterial pressure at rest(Baseline, 12 months)
- Change in pulmonary arterial pressure at exercise(Baseline, 12 months)
- Change in right atrial pressure(Baseline, 12 months)
- Change in cardiac output(Baseline, 12 months)
- Change in pulmonary vascular resistance from rest to peak exercise(Baseline, 12 months)
研究者
Barry Borlaug
Principal Investigator
Mayo Clinic
研究点 (1)
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