- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04082442
Evolocumab in Patients With Acute MI (EVACS II)
Evolocumab in Patients With Acute Myocardial Infarction: A Double-blind, Prospective, Randomized Placebo-Controlled Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Despite aggressive early intervention and current secondary prevention strategies, many patients who survive hospitalization for an acute coronary syndrome (ACS) experience subsequent unfavorable outcomes, including recurrent ischemic events and unfavorable cardiac remodeling associated with progressive left ventricular dysfunction and congestive heart failure. Vascular and myocardial inflammation are significantly increased in ACS patients, are closely correlated with LDL-C levels, and are associated with these adverse consequences. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in patients with ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of evolocumab to current medical therapies may therefore be of particular benefit in these patients, by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.
In this study, the investigators propose to test the effects of PCSK9 inhibition with evolocumab on LDL-C reduction, vascular and myocardial inflammation, cardiac function, and clinical outcomes in an ACS patient cohort.
The investigators propose a double-blind randomized study of 100 patients presenting with an ACS (ST-Elevation- and Non-ST-elevation myocardial infarction). One hundred ACS patients will be randomized to evolocumab, 420 mg or to placebo (50 in each group) during early hospitalization and will also receive current guideline-directed ACS therapy. Lipid profiles, including LDL-cholesterol levels, and traditional and novel serum markers of inflammation and endothelial function will be measured at presentation, during the index hospitalization, and at 30-day and six-month follow-up. Positron Emission Tomography (PET) scans to measure myocardial and vascular inflammation and echocardiograms will be performed during the early post-infarction period and at thirty days (PET and echocardiogram) and six-month (echocardiogram) following randomization. Clinical outcomes, such as angina class, will also be collected at the six-month follow-up visit.
The protocol and the primary and secondary lipid and inflammatory outcomes in this study are identical to those in NCT03515304 and therefore the data in the two studies may be analyzed together.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21287
- The Johns Hopkins Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 25 to 90 years.
- ST elevation myocardial infarction, with compatible symptoms and ECG changes.
- Non ST elevation myocardial infarction, with a troponin I > 5ng/mL and with compatible symptoms and ECG changes.
- Permission of attending physician.
- Ability to understand the risk, benefits, and alternatives of participation.
Exclusion Criteria:
- Scheduled for cardiac surgery.
- Current treatment with a PCSK9 antibody.
- Current participation in an intervention clinical trial.
- Latex allergy
- Previous adverse reaction to monoclonal antibodies
- Non-English speaking
Female of childbearing potential. This is a female subject who has not used acceptable method(s) of birth control (see below) for at least one month prior to screening, unless the subject is sterilized or postmenopausal. Menopause is defined as: 12 months of spontaneous and continuous amenorrhea in a female > 55 year of age.
Acceptable method(s) of birth control definition: One highly effective method (methods that can achieve a failure rate of less than 1% per year when used consistently and correctly)
- Combined hormonal (estrogen and progestogen) contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
- Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence
- Subject likely not to be available to complete all protocol-related study visits or procedures.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Evolocumab
420 mg evolocumab administered subcutaneously using an autoinjector/pen in ACS patients.
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420 mg evolocumab.
|
Placebo Comparator: Placebo
Placebo administered subcutaneously using an autoinjector/pen in ACS patients .
|
Matching placebo.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in LDL-Cholesterol
Time Frame: Baseline, 25-30 days
|
The difference, in the percent change in LDL-cholesterol (mg/dL), from pre-randomization to the 25-30 day values between the evolocumab and placebo groups.
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Baseline, 25-30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in PET Imaging for inflammation
Time Frame: Baseline, 30 days
|
The change between early infarction period and thirty day assessments of i. PET-FDG assessed vascular inflammation in the most diseased segment of aorta or carotid artery ii.
PET-FDG assessed myocardial inflammation
|
Baseline, 30 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Thorsten Leucker, MD, PhD, Johns Hopkins University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Acute Coronary Syndrome
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Protease Inhibitors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Serine Proteinase Inhibitors
- PCSK9 Inhibitors
- Evolocumab
Other Study ID Numbers
- IRB00206305
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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