EVACS II: Evolocumab in Patients With Acute MI

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04082442
• Collaborator: Amgen (Industry), Washington University School of Medicine (Other)
• Enrollment: 100
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 39
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in 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 the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in patients with an ACS by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Evolocumab; Drug: Placebos	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evolocumab in Patients With Acute Myocardial Infarction: A Double-blind, Prospective, Randomized Placebo-Controlled Study
• Actual Study Start Date: Sep 1, 2019
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Evolocumab 420 mg evolocumab administered subcutaneously using an autoinjector/pen in ACS patients.	Drug: Evolocumab; 420 mg evolocumab.
Placebo Comparator: Placebo Placebo administered subcutaneously using an autoinjector/pen in ACS patients .	Drug: Placebos; Matching placebo.

Outcome Measures

Primary Outcome Measures

1. Change in LDL-Cholesterol [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.

Secondary Outcome Measures

1. Change in PET Imaging for inflammation [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 25 to 90 years.

2. ST elevation myocardial infarction, with compatible symptoms and ECG changes.

3. Non ST elevation myocardial infarction, with a troponin I > 5ng/mL and with compatible symptoms and ECG changes.

4. Permission of attending physician.

5. Ability to understand the risk, benefits, and alternatives of participation.

Exclusion Criteria:

1. Scheduled for cardiac surgery.

2. Current treatment with a PCSK9 antibody.

3. Current participation in an intervention clinical trial.

4. Latex allergy

5. Previous adverse reaction to monoclonal antibodies

6. Non-English speaking

7. 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

1. Subject likely not to be available to complete all protocol-related study visits or procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University
• Amgen
• Washington University School of Medicine

Investigators

• Principal Investigator: Thorsten Leucker, MD, PhD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT04082442
• Other Study ID Numbers: IRB00206305
• First Posted: Sep 9, 2019
• Last Update Posted: Jun 21, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Acute Coronary Syndrome; Evolocumab

Study Results

No Results Posted as of Jun 21, 2022