Evolocumab or Normal Strategies to Reach LDL Objectives in Acute Myocardial Infarction Upbound to PCI (AMUNDSEN)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: NSTEMI - Non-ST Segment Elevation MI; STEMI - ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Standard of care (SOC); Drug: Evolocumab 140 MG/ML

Detailed Description

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
• Enrollment (Estimated): 2166
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • ACTION Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participant meeting all of the following criteria will be considered for enrolment into the trial:

1. 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:

   • Age≥18
   • 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
2. 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
3. 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:

1. Fibrinolysis treatment
2. Planned CABG

3. 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%
4. Evidence of severe hepatobiliary disease: current active hepatic dysfunction or active biliary obstruction, decompensated cirrhosis or infectious/inflammatory hepatitis
5. Active malignancy
6. A comorbid condition with an estimated life expectancy of ≤ 12 months
7. Previously received or receiving evolocumab or any other therapy to inhibit PCSK9
8. Known sensitivity to any of the products or components to be administered during trial
9. 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
10. 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.
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care (SOC); management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria	Drug: Standard of care (SOC); management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria
Experimental: 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.	Drug: Evolocumab 140 MG/ML; Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 36 months.; Other Names: Repatha

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	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
Lipoprotein(a) (Lp(a)	Monitoring of (Lp(a)	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	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
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)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Amgen; Action Research Group
• Investigators: Principal Investigator: Gilles MONTALESCOT, Pr, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2021
• Primary Completion (Estimated): May 22, 2026
• Study Completion (Estimated): May 22, 2028

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: June 26, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PCI; STEMI; LDL-C; NSTEMI; STATIN; EVOLOCUMAB; Anti-PCSK9
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; evolocumab
• Other Study ID Numbers: APHP201075; 2021-000573-80 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No