Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI): a Randomized Controlled Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Difference in the change of left ventricular ejection fraction (LVEF)
研究概览
简要总结
This study evaluates the off-target effect of paroxetine to reverse cardiac remodeling and improve left ventricular ejection fraction in patients after acute myocardial infarction. Half of the participants will receive paroxetine, while the other half will receive placebo treatment.
详细描述
Cardiac remodeling is characterized by a composite of structural, geometric, molecular, and functional changes of the myocardium, and is an important determinant of heart failure and cardiovascular outcome in survivors of acute myocardial infarction. Progression of heart failure secondary to the remodeling process results from dysregulation of the G protein-coupled receptor (GPCR). Excessive adrenergic drive in patients with heart failure results in an enhanced activation of GPCR kinases (GRKs) that is considered to have a central role in adverse cardiac remodeling after ischemic injury. The selective Serotonin reuptake inhibitor paroxetine specifically binds to the catalytic domain of GRK2 as an off-target effect, and has been shown to reverse cardiac remodeling and increase left ventricular ejection fraction in a mouse model. The effect was observed at serum levels achieved with standard dosages of paroxetine, and was robust in mice with and without concomitant heart failure treatment, respectively.
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
- •Anterior wall ST-segment elevation myocardial infarction
- •Primary percutaneous coronary intervention (PCI) within 24 hours of symptom onset
- •Left ventricular ejection fraction ≤ 45% within 48-96 hours after primary PCI (transthoracic echocardiography)
排除标准
- •Female patients at reproductive age (<50 years)
- •Known intolerance to paroxetine
- •Inability to provide informed consent
- •Currently participating in another trial before reaching first endpoint
- •Current medical therapy with MAO-blocker (during, 14 days before, and 14 days after treatment with MAO-blocker), lithium, thioridazide, or pimozide
- •Concomitant tamoxifen intake
- •Previous myocardial infarction
- •Previous revascularization procedure (percutaneous coronary intervention or coronary artery bypass grafting).
- •Contraindication to cardiac magnetic resonance imaging
- •Obvious or questionable inability to appropriately cooperate (alcohol, drugs etc.)
- •Relevant nephropathy or hepatopathy
研究组 & 干预措施
Paroxetine
Paroxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week
干预措施: Paroxetine (Drug)
Placebo
Placebo oral capsule QD per os for 13 weeks
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Difference in the change of left ventricular ejection fraction (LVEF)
时间窗: 12 weeks after randomization
Assessment by cardiac magnetic resonance imaging
次要结局
- Difference in change in left left-ventricular end-systolic volume (LVESV)(12 weeks after randomization)
- Difference in LVEF between baseline and 12 weeks, and 12 months, respectively(12 months after randomization)
- Major adverse cardiac events(12 weeks and 12 months after randomization)
- Difference in change in left left-ventricular end-diastolic volume (LVEDV)(12 weeks after randomization)
- Difference in late-enhancement(12 weeks after randomization)
- Clinical symptoms of heart failure(12 weeks and 12 months after randomization)