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

Primary Purpose

STEMI - ST Elevation Myocardial Infarction, NSTEMI - Non-ST Segment Elevation MI

Status
Unknown status
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Evolocumab 140 MG/ML
Standard of care (SOC)
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for STEMI - ST Elevation Myocardial Infarction focused on measuring STEMI, NSTEMI, PCI, STATIN, EVOLOCUMAB, Anti-PCSK9, LDL-C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

  1. Male or female
  2. 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

    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 study 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
  3. Statin at maximal tolerated dose, as part of the standard of care at randomization
  4. Informed consent obtained in writing at enrolment into the study

Exclusion Criteria:

Participant presenting with any of the following will not be included in the study:

  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 study
  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 study, or less than 30 days since ending treatment on another investigational device or drug study(ies).
  11. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.

Sites / Locations

  • ACTION Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Evolocumab + SOC

Standard of care (SOC)

Arm Description

Investigational Product is open label Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 12 months.

management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
LDL-C reduction of ≥ 50% and an LDL-C goal of <1.4 mmol/L (<55 mg/dL)
Monitoring of changes in LDL-C levels
Percent change in levels of LDL-C
Monitoring of changes in LDL-C levels
Time to achieve LDL-C target
Monitoring of changes in LDL-C levels
Time averaged LDL-C change
Monitoring of changes in LDL-C levels
Change on total cholesterol
Monitoring of changes in cholesterol levels
Change on HDL-C
Monitoring of changes in HDL-C levels
Change on triglycerides
Monitoring of changes in triglycerides levels
Change on non-HDL-C
Monitoring of changes in non-HDL-C levels

Full Information

First Posted
May 27, 2021
Last Updated
October 1, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Action Research Group, Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT04951856
Brief Title
Evolocumab or Normal Strategies to Reach LDL Objectives in Acute Myocardial Infarction Upbound to PCI
Acronym
AMUNDSEN
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
September 29, 2021 (Actual)
Primary Completion Date
September 29, 2023 (Anticipated)
Study Completion Date
September 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Action Research Group, Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
STEMI - ST Elevation Myocardial Infarction, NSTEMI - Non-ST Segment Elevation MI
Keywords
STEMI, NSTEMI, PCI, STATIN, EVOLOCUMAB, Anti-PCSK9, LDL-C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1666 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Evolocumab + SOC
Arm Type
Experimental
Arm Description
Investigational Product is open label Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 12 months.
Arm Title
Standard of care (SOC)
Arm Type
Active Comparator
Arm Description
management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria
Intervention Type
Drug
Intervention Name(s)
Evolocumab 140 MG/ML
Other Intervention Name(s)
Repatha
Intervention Description
Evolocumab (Repatha®) 140 mg every two weeks: first subcutaneous injection at the time of randomization, before PCI, followings during 12 months.
Intervention Type
Drug
Intervention Name(s)
Standard of care (SOC)
Intervention Description
management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria
Primary Outcome Measure Information:
Title
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.
Description
Monitoring of changes in LDL-C levels
Time Frame
From baseline and at 12 months
Secondary Outcome Measure Information:
Title
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.
Description
The same rules as above for the primary endpoint, will apply.
Time Frame
From baseline and at 12 months
Title
LDL-C reduction of ≥ 50% and an LDL-C goal of <1.4 mmol/L (<55 mg/dL)
Description
Monitoring of changes in LDL-C levels
Time Frame
From baseline to 6 weeks and 22 weeks
Title
Percent change in levels of LDL-C
Description
Monitoring of changes in LDL-C levels
Time Frame
From baseline to 6 weeks, 22 weeks and 12 months
Title
Time to achieve LDL-C target
Description
Monitoring of changes in LDL-C levels
Time Frame
Up to 12 months
Title
Time averaged LDL-C change
Description
Monitoring of changes in LDL-C levels
Time Frame
Up to 12 months
Title
Change on total cholesterol
Description
Monitoring of changes in cholesterol levels
Time Frame
At baseline, 6 weeks, 22 weeks and 12 months
Title
Change on HDL-C
Description
Monitoring of changes in HDL-C levels
Time Frame
At baseline, 6 weeks, 22 weeks and 12 months
Title
Change on triglycerides
Description
Monitoring of changes in triglycerides levels
Time Frame
At baseline, 6 weeks, 22 weeks and 12 months
Title
Change on non-HDL-C
Description
Monitoring of changes in non-HDL-C levels
Time Frame
At baseline, 6 weeks, 22 weeks and 12 months
Other Pre-specified Outcome Measures:
Title
Composite of death or any hospitalization for a Cardiovascular (CV) reason
Description
Data obtained from reported adverse events occurred during participation to the study
Time Frame
Up to 12 months
Title
Composite of death, MI, stroke, unplanned revascularization
Description
Data obtained from reported adverse events occurred during participation to the study
Time Frame
Up to 12 months
Title
Individual endpoints of the composite endpoint above (death, MI, Stroke, unplanned revascularization)
Description
Data obtained from reported adverse events occurred during participation to the study
Time Frame
Up to 12 months
Title
Pooled analysis of relationship between time to achieve LDL-C goal and death or any hospitalization for a CV reason
Description
Data obtained from reported adverse events occurred during participation to the study and LDL-C levels
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant meeting all of the following criteria will be considered for enrolment into the study: Male or female 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 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 study 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 Informed consent obtained in writing at enrolment into the study Exclusion Criteria: Participant presenting with any of the following will not be included in the study: 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 study 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 study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilles MONTALESCOT, Pr
Phone
01 42 16 30 07
Ext
00 33
Email
gilles.montalescot@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilles MONTALESCOT, Pr
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
ACTION Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMC
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gilles MONTALESCOT, Pr
Phone
01 42 16 30 07
Ext
0033
Email
gilles.montalescot@aphp.fr

12. IPD Sharing Statement

Learn more about this trial

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

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