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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000573-80 | EudraCT Number |
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| Name | Class |
|---|---|
| Action Research Group | OTHER |
| Amgen | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Evolocumab + SOC | Experimental | 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. |
|
| Standard of care (SOC) | Active Comparator | management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab 140 MG/ML | Drug | Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 36 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | Frome randomization to 12 months follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| LDL-C<40mg/dL at 12 months follow-up | Monitoring of changes in LDL-C levels (endpoints tested in hierarchical order) | from baseline and at 12 months follow-up |
| Composite of death (any cause), MI, stroke, unplanned revascularization |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | The same rules as above for the primary endpoint, will apply. | From baseline and at 12 months |
| LDL-C reduction of ≥ 50% and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) in the overall population |
Inclusion Criteria:
Participant meeting all of the following criteria will be considered for enrolment into the trial:
Diagnosis of STEMI or NSTEMI
STEMI defined as:
NSTEMI defined as:
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
Exclusion Criteria:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Gilles MONTALESCOT, Pr | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ACTION Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMC | Paris | 75013 | France |
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|
| Standard of care (SOC) | Drug | management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria |
|
Data obtained from reported adverse events occurred during participation to the study (endpoints tested in hierarchical order)
| 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) | 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) | 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) | 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) | from randomization to 12 months follow-up |
Monitoring of changes in LDL-C levels |
| From baseline and end-of-follow-up (longest follow up for each patient, up to 3 years) |
| Composite endpoint of death or any hospitalization for a Cardiovascular (CV) reason | Data obtained from reported adverse events occurred during participation to the study | At longest follow-up for each patient, up to 3 years |
| LDL-C<40mg/dL at longest follow-up | Monitoring of changes in LDL-C levels | At longest follow up for each patient, assessed up to 3 years |
| Composite of death (any cause), MI, stroke, unplanned revascularization | Data obtained from reported adverse events occurred during participation to the study | At longest follow up for each patient, assessed up to 3 years |
| Composite of death (any cause), MI, stroke | Data obtained from reported adverse events occurred during participation to the study | At longest follow up for each patient, assessed up to 3 years |
| Composite of death (any cause) or myocardial infarction | Data obtained from reported adverse events occurred during participation to the study | At longest follow up for each patient, assessed up to 3 years |
| Death (any cause) | Data obtained from reported adverse events occurred during participation to the study | At longest follow up for each patient, assessed up to 3 years |
| Death (cardiovascular) | Data obtained from reported adverse events occurred during participation to the study | At longest follow up for each patient, assessed up to 3 years |
| Percent change in levels of LDL-C | Monitoring of changes in LDL-C levels | From baseline to 12 months, and at longest follow up for each patient, assessed up to 3 year |
| Time to achieve LDL-C target | Monitoring of changes in LDL-C levels | Over 12 months and over longest follow up for each patient, assessed up to 3 year |
| Time averaged LDL-C change | Monitoring of changes in LDL-C levels | Over 12 months and over longest follow up for each patient, assessed up to 3 years |
| Change on total cholesterol | Monitoring of changes in cholesterol levels | From baseline and at 12 months and at longest follow up for each patient, assessed up to 3 year |
| Change on HDL-C | Monitoring of changes in HDL-C levels | From baseline and at 12 months and at longest follow up for each patient, assessed up to 3 year |
| Change on triglycerides | Monitoring of changes in triglycerides levels | From baseline and at 12 months and at longest follow up for each patient, assessed up to 3 year |
| Change on non-HDL-C | Monitoring of changes in non-HDL-C levels | From baseline and at 12 months and at longest follow up for each patient, assessed up to 3 year |
| Lipoprotein(a) (Lp(a) | Monitoring of (Lp(a) | at 12 months. |
| Pooled analysis of relationship between time to achieve LDL-C goal and death or any hospitalization for a CV reason | Data obtained from reported adverse events occurred during participation to the study and LDL-C levels | At longest follow up for each patient, assessed up to 3 years |
| LDL-C reduction with a final LDL-C of <1.0 mmol/L (<40 mg/dL), in the global population and in patients who experienced a second vascular event within 2 years before randomization including the index event while taking maximally tolerated statin | Monitoring of changes in LDL-C levels | Longest follow-up (up to 3 years) |
| ID | Term |
|---|---|
| D000072657 | ST Elevation Myocardial Infarction |
| D000072658 | Non-ST Elevated Myocardial Infarction |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
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| ID | Term |
|---|---|
| C577155 | evolocumab |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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