Recombinant Human Interleukin-1 Receptor Antagonist, Anakinra, to Prevent Post-infarction Remodeling: the Virginia Commonwealth University Anakinra Remodeling Trial (VCU-ART)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Difference Between the Anakinra Arm and Placebo Arm in Change in End-systolic Volume Indices From Baseline to Follow up Exam 10-14 Weeks Later at Cardiac Magnetic Resonance Imaging.
研究概览
简要总结
Thousands of patients die daily from early and late complications of a heart attack (acute myocardial infarction, AMI). Patients surviving AMI remain at high risk of death from adverse cardiac remodeling (dysfunction and enlargement of the heart) leading to heart failure (weakening of the heart).
Current interventions proven to reduce adverse remodeling and progression to heart failure include early reperfusion (restoring blood flow to the heart muscle) and long-term use of medicines that block the effects of hormones (such as angiotensin II, norepinephrine and aldosterone) involved in adverse remodeling. Despite these treatments, however, many patients continue to develop heart failure within 1 year of AMI. These patients are at very high risk of death.
Numerous changes occur in the hearts of patients after AMI that lead to adverse remodeling. Ischemia (lack of oxygen) and infarction (cell damage) lead to increased interleukin-1 (IL-1) production in the heart. IL-1 plays a critical role in adverse cardiac remodeling by coordinating the inflammatory pathway (leading to wound healing) and apoptotic pathway (leading to cell death).
In opposition to IL-1 activity, the human body produces a natural IL-1 receptor antagonist that blocks the effects of IL-1. The drug form of this IL-1 receptor antagonist (anakinra) is currently FDA approved for the treatment of rheumatoid arthritis, an inflammatory disease characterized by excessive IL-1 activity. Experimental studies show that anakinra is able to prevent cardiac remodeling and improve survival in mice after AMI.
We hypothesize that anakinra will show similar benefits in human patients by preventing adverse remodeling and heart failure after AMI.
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)
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
- •Age >18 years
- •Acute (<24 hours) onset of chest pain
- •New or presumably new ST elevation on ECG
- •Planned coronary angiography for percutaneous revascularization
排除标准
- •Inability to give informed consent
- •Late presentation (>24 hours)
- •Unsuccessful revascularization or urgent coronary bypass surgery
- •Hemodynamic instability
- •End-stage congestive heart failure (AHA/ACC stage C/D, NYHA class IV)
- •Preexisting severe LV dysfunction (LVEF<20%) or severe valvular disease
- •Severe asthma
- •Pregnancy ( pre-enrollment pregnancy test)
- •Contraindications to cardiac MRI or cardiac angiography
- •Severe coagulopathy (INR>2.0, Platelet count<50,000/mm3)
- •Severe renal insufficiency (creatinine clearance <30 ml/min/m2)
- •Recent (<14 days) use of anti-inflammatory drugs (NSAIDS excluded)
- •Chronic inflammatory disease
研究组 & 干预措施
Anakinra
Anakinra 100 mg given daily by subcutaneous injection for 14 days
干预措施: Anakinra (Drug)
Placebo
0.67 ml of NaCl 0.9% solution
干预措施: Placebo (Drug)
结局指标
主要结局
Difference Between the Anakinra Arm and Placebo Arm in Change in End-systolic Volume Indices From Baseline to Follow up Exam 10-14 Weeks Later at Cardiac Magnetic Resonance Imaging.
时间窗: 10-14 weeks
次要结局
未报告次要终点