The Effect of Early Administration of PCSK9 Inhibitor, Alirocumab to Acute Ischemic Stroke Patients Associated With Atherosclerosis on the Stroke Prognosis and Lipid Profile, a Single Center Study, Registry Based, Pragmatic, Prospective Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- LDL change rate
研究概览
简要总结
The goal of this clinical trial is to test the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors) in acute ischemic stroke patients associated with atherosclerosis by investigating
- the change in lipid profile compared to baseline results
- the effects on prognosis of stroke The participants will be given PCSK9 inhibitor right after confirmation of acute ischemic stroke, and the investigators will compare the results to the control group, whom are acute ischemic stroke patients treated with conventional lipid lowering therapy, statin and/or ezetimibe.
详细描述
This clinical trial will be recommended to patients aged 19 and older who are admitted with ischemic stroke accompanied by atherosclerosis of large arteries, rather than cardiac embolism. Upon confirmation of ischemic stroke through CT and MRI in the emergency room, the patient will be provided with a detailed explanation of the future treatment plan and the purpose of this study.
Depending on the day of the week, the patient will be randomly assigned to the treatment group (alirocumab + high-dose statin group) and the control group (high-dose statin group) in a 1:1 ratio.
For those in the treatment group, alirocumab (brand name: Praluent Pen) 300mg will be administered as a single dose. Both the treatment and control groups will receive standard diagnostic tests and treatments as conventional stroke patients unrelated to the clinical trial. Blood samples collected for testing will be promptly discarded by the hospital's diagnostic laboratory. Both groups will have outpatient visits one month after discharge.
The investigators are planning on total 200 patients enrollment (100 treatment group + 100 control group).
For categorical variables, frequency and percentage will be provided, and for continous variables, mean and standard deviation will be provided. All statistical tests used for analysis will be two-tailed. Statistical significance will be tested at a 5% significance level. If necessary, two-sided 95% confidence intervals will be provided.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-cardioembolic Stroke
- •Acute Ischemic stroke within 7 days of symptom onset (confirmed by CT or MRI)
- •Age 19 and above
- •Significant stenosis associated with atherosclerosis in major intracranial / extracranial vessels.
- •National Institutes of Health Stroke Scale(NIHSS) score of 15 or less at admission
- •Patients with the capacity to consent for participation in the clinical trial.
排除标准
- •Presence of high-risk factors for cardioembolism
- •Risk of ischemic stroke due to thrombosis from other causes
- •Patients with hemorrhagic stroke, brain tumors, or brain abscesses
- •Patients unable to take statins or PCSK9 inhibitors
- •Pre-stroke mRS score of 3 or higher
- •Severe liver failure (liver enzyme > 3 times the upper normal limit) or renal failure (serum Creatinine > 2mg/dL or estimated glomerular filtration rate < 30 mL/min/1.73m2)
- •Anemia (hemoglobin < 8mg/dL) or thrombocytopenia (platelet count < 100K)
- •Uncontrolled diabetes not managed by medication or insulin
- •Pregnant or breastfeeding patients
- •Patients already receiving PCSK-9 inhibitors
- •Patients deemed inappropriate for participation in the clinical trial by the investigator for other reasons.
研究组 & 干预措施
Alirocumab
The treatment group patients will receive an additional PCSK9 inhibitor (alirocumab 300mg once) at emergency departement in addition to statin therapy, which is conventional medication given for acute ischemic stroke.
干预措施: Alirocumab (Drug)
结局指标
主要结局
LDL change rate
时间窗: LDL level at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
The change rate of LDL in PCSK9 inhibitor treated group (alirocumab group) compared to standard of care group.
Achievement rate to target LDL level
时间窗: LDL target achievement rate at day-1 of hospitalization, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).
The investigators intend to use 3 different criteria - 1. LDL under 70mg/dl 2. LDL under 55mg/dL 3. LDL decrement over 50% compared to baseline (day0 LDL)
次要结局
- Change of Lipoprotein-A(Lipoprotein-A are collected at day-1, once.)
- Change of total cholesterol(TC)(TC levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).)
- Change triglyceridTG)(TG levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).)
- Change of High density lipoprotein(HDL)(HDL levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).)
- Change of Apolipoprotein-B(Apolipoprotein-B is collected at day-1, once.)
- The difference between admission and discharge - 2(NIHSS score is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).)
- The rate of complications of statin - 2(Laboratory tests for alanine transaminase (ALT, IU/L) and investigations of possible complication symptoms (abdominal pain or tenderness, fatigue, nausea/vomiting, etc) will be done at outpatient follow up date (day-30).)
- The rate of complications of statin - 3(Laboratory tests for aspartate transaminase (AST, IU/L) and investigations of possible complication symptoms (abdominal pain or tenderness, fatigue, nausea/vomiting, etc) will be done at outpatient follow up date (day-30).)
- The rate of complications of statin -4(Laboratory tests (myoglobin, ng/mL) and investigations of possible complication symptoms (muscle pain or fatigue, tenderness) will be done at outpatient follow up date (day-30).)
- The rate of complications of statin -5(Laboratory tests (creatine kinase, IU/L) and investigations of possible complication symptoms (muscle pain or fatigue, tenderness) will be done at outpatient follow up date (day-30).)
- The recurrence rate(The event rate until the outpatient follow up date (up to 1 month, day-30).)
- The rate of complications of statin - 1(Laboratory tests for hemoglobin A1c (%) will be done at outpatient follow up date (day-30).)
- The patient's outcome - 1(mRS is calculated when patients are discharged from neurology department(normally day-5 to day-7), and when patients come to outpatient department (day-30).)
- The patient's outcome - 2(NIHSS score is calculated when patients are discharged from neurology department(normally day-5 to day-7), and when patients come to outpatient department (day-30).)
- The difference between admission and discharge - 1(mRS is assessed when patients are admitted(day-0), and when patients are discharged(normally day-5 to day-7).)
- Early neurological deterioration(The drop of NIHSS score in initial period (72 hours) during admission.)
- The expansion of stroke lesion(The follow up MRI is routinely taken at day-1 or day-2 of hospitalization.)
研究者
Sun U. Kwon
Professor
Asan Medical Center