Acute Myocardial Infarction Upbound to PCI Immediately (STEMI) or in the Next Three Days (NSTEMI), and Randomized to Subcutaneous Evolocumab or Normal Strategies to Reach Guidelines LDL Objectives in the Real-world - The AMUNDSEN-real Study
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 2,166
- 试验地点
- 2
- 主要终点
- LDL-C reduction of ≥ 50% from baseline and a final LDL-C of <1.4 mmol/L (<55 mg/dL) at 12 months follow-up.
研究概览
简要总结
AMUNDSEN-real is a phase IV, international (7 European countries), multicenter, controlled, open label study randomized, in 2 parallel groups of patients with a diagnosis of STEMI or NSTEMI with an indication for PCI, using the PROBE study design (Prospective Randomised Open, Blinded Endpoint).
The objective of this study is to demonstrate the superiority of evolocumab versus standard of care in reaching a LDL-C reduction of ≥ 50% from baseline and a LDL-C goal of <1.4 mmol/L (<55 mg/dL) at 12 months follow-up on the overall population.
The primary clinical objective is to demonstrate the superiority of evolocumab versus standard of care on the composite endpoint of death or any unplanned hospitalization for a CV reason at 12 months.
Central randomization uses an IWRS. Stratification is by center and stratum with random block size, generated according to the procedures of the sponsor, by a statistician not involved in the study.
详细描述
Previous randomized studies and several meta-analyses have shown a positive effect of high-dose statins pretreatment on peri-procedural Myocardial Infarction (MI) incidence with favorable trends on mortality in both Acute Coronary Syndrome (ACS) and stable Coronary Artery Disease patients.
Numerous epidemiological studies, Mendelian randomization studies, and Randomized Controled Trials have consistently demonstrated a log-linear relationship between the absolute changes in plasma LDL-C and the risk of Cardio-Vascular (CV) disease. The effect of LDL-C on the risk of a new CV event appears to be determined by the absolute magnitude, the duration of exposure to LDL-C and possibly the time to reach the recommended target of low LDL in ACS patients.
There are good reasons to believe that the Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors could provide additional benefits when used early in MI patients treated with PCI revascularization.
That's why the hypothesis of AMUNDSEN study is to demonstrate the superiority of a strategy using evolocumab before PCI in STEMI or NSTEMI patients versus standard of care (SOC) as described in the 2019 European Society of Cardiology / European Atherosclerosis Society (ESC/EAS) guidelines on dyslipidemia, to reach a Low-Density Lipoprotein Cholesterol (LDL-C) reduction of ≥ 50% from baseline and a LDL-C goal of <1.4 mmol/L (<55 mg/dL) at the end of the study (LDL targets of the 2019 ESC/EAS guidelines).
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
- None
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
- •Participant meeting all of the following criteria will be considered for enrolment into the trial:
- •Diagnosis of STEMI or NSTEMI
- •STEMI defined as:
- •symptoms of acute MI of at least 30 min AND
- •within the previous 24 hours with new persistent ST-segment elevation ≥1 mm in ≥2 continuous ECG leads AND
- •an indication for primary PCI AND
- •> 55 years reported by the patient
- •NSTEMI defined as:
- •a history of chest discomfort or ischemic symptoms of ≥10 minutes duration at rest ≤48 hours prior to entry into the trial with no evidence of persistent ST-segment elevation and with an elevated troponin (≥ the upper limit of normal according to local laboratory norms), AND
- •indication for a coronary angiogram within 72hrs AND
- •indication for PCI AND
- •at least one the following high-risk characteristics: Diabetes Peripheral Artery Disease Multivessel (≥ 2 or LM) disease on the coronary angiogram History of MI or stroke without sequels prior to randomization eGFR: 15 to 45 mL/min/1.73 m2 calculated with MDRD formula at randomization
- •Statin at maximal tolerated dose, as part of the standard of care at randomization, means Intent to treat with statin and the patient will receive his first dose as soon as possible after admission
- •Informed consent obtained in writing at enrolment into the trial
排除标准
- •Participant presenting with any of the following will not be included in the trial:
- •Fibrinolysis treatment
- •Planned CABG
- •Ongoing hemodynamic instability defined as any of the following:
- •Killip Class III or IV
- •Sustained and/or symptomatic hypotension (systolic blood pressure < 80 mm Hg)
- •Known left ventricular ejection fraction < 30%
- •Evidence of severe hepatobiliary disease: current active hepatic dysfunction or active biliary obstruction, decompensated cirrhosis or infectious/inflammatory hepatitis
- •Active malignancy
- •A comorbid condition with an estimated life expectancy of ≤ 12 months
- •Previously received or receiving evolocumab or any other therapy to inhibit PCSK9
- •Known sensitivity to any of the products or components to be administered during trial
- •Female subject is pregnant, had a positive pregnancy test at inclusion, breastfeeding, or planning to become pregnant or breastfeed during treatment and for an additional 17 weeks after the last dose of IMP
- •Currently receiving treatment in any other investigational device or drug trial, or less than 30 days since ending treatment on another investigational device or drug trial.
- •Participant likely to not be available to complete all protocol-required trial visits or procedures, and/or to comply with all required trial procedures to the best of the participant and investigator's knowledge.
研究组 & 干预措施
Standard of care (SOC)
management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria
干预措施: Standard of care (SOC) (Drug)
Evolocumab + SOC
Investigational Product is open label Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 36 months.
干预措施: Evolocumab 140 MG/ML (Drug)
结局指标
主要结局
LDL-C reduction of ≥ 50% from baseline and a final LDL-C of <1.4 mmol/L (<55 mg/dL) at 12 months follow-up.
时间窗: From baseline and at 12 months
Monitoring of changes in LDL-C levels
LDL-C reduction of ≥ 50% from baseline and a final LDL-C of <1.4 mmol/L (<55 mg/dL) at 12 months follow-up
时间窗: From baseline and at 12 months
Monitoring of changes in LDL-C levels
Composite endpoint of death (any cause) or any unplanned hospitalization for a CV reason
时间窗: Frome randomization to 12 months follow-up
Main clinical endpoint obtained from reported adverse events occurred during participation to the study
次要结局
- Time averaged LDL-C change(Up to 12 months, at 24 months, and end of follow-up(longest follow up for each patient))
- Change on non-HDL-C(At baseline, 6 weeks, 22 weeks, 12, 24 months, and end of follow-up(longest follow up for each patient))
- Change on HDL-C(At baseline, 6 weeks, 22 weeks , 12, 24 months, and end of follow-up(longest follow up for each patient))
- Lipoprotein(a) (Lp(a)(at 12 months.)
- Change on triglycerides(At baseline, 6 weeks, 22 weeks, 12, 24 months, and end of follow-up(longest follow up for each patient))
- Percent change in levels of LDL-C(From baseline to 6 weeks, 22 weeks, 12, 24 months, and end of follow-up(longest follow up for each patient))
- Change on total cholesterol(At baseline, 6 weeks, 22 weeks, 12, 24 months, and end of follow-up(longest follow up for each patient))
- LDL-C reduction of ≥ 50% from baseline and a final LDL-C of <1.4 mmol/L (<55 mg/dL) at 12 months follow-up, country by country.(From baseline and at 12 months)
- LDL-C reduction of ≥ 50% and an LDL-C goal of <1.4 mmol/L (<55 mg/dL)and other relevant thresholds: <70, <40, and <20 mg/dL(From baseline to 6 weeks and 22 weeks, 12, 24 months and end-of-follow-up(longest follow up for each patient))
- Time to achieve LDL-C target(Up to 12 months)
- Composite of death (any cause), MI, stroke(from randomization to 12 months follow-up)
- LDL-C<40mg/dL at 12 months follow-up(from baseline and at 12 months follow-up)
- Composite of death (any cause), MI, stroke, unplanned revascularization(from randomization to 12 months follow-up)
- Composite of death (any cause) or myocardial infarction(from randomization to 12 months follow-up)
- Death (any cause)(from randomization to 12 months follow-up)
- Death (cardiovascular)(from randomization to 12 months follow-up)