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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,166
Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 36 months.
management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria
ACTION Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMC
Paris, France
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
Monitoring of changes in LDL-C levels
Time frame: From baseline and at 12 months
Composite endpoint of death (any cause) or any unplanned hospitalization for a CV reason
Main clinical endpoint obtained from reported adverse events occurred during participation to the study
Time frame: Frome randomization to 12 months follow-up
LDL-C<40mg/dL at 12 months follow-up
Monitoring of changes in LDL-C levels (endpoints tested in hierarchical order)
Time frame: from baseline and at 12 months follow-up
Composite of death (any cause), MI, stroke, unplanned revascularization
Data obtained from reported adverse events occurred during participation to the study (endpoints tested in hierarchical order)
Time frame: from randomization to 12 months follow-up
Composite of death (any cause), MI, stroke
Data obtained from reported adverse events occurred during participation to the study (endpoints tested in hierarchical order)
Time frame: from randomization to 12 months follow-up
Composite of death (any cause) or myocardial infarction
Data obtained from reported adverse events occurred during participation to the study (endpoints tested in hierarchical order)
Time frame: from randomization to 12 months follow-up
Death (any cause)
Data obtained from reported adverse events occurred during participation to the study (endpoints tested in hierarchical order)
Time frame: from randomization to 12 months follow-up
Death (cardiovascular)
Data obtained from reported adverse events occurred during participation to the study (endpoints tested in hierarchical order)
Time frame: from randomization to 12 months follow-up
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