Evolocumab in Acute Coronary Syndrome (EVACS)

October 25, 2023 updated by: Johns Hopkins University

Evolocumab in Acute Coronary Syndrome: A Double-Blind Randomized Placebo Controlled Study

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 an important subset of ACS patients, those with non-ST elevation myocardial infarction (NSTEMI) by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.

Study Overview

Status

Active, not recruiting

Intervention / Treatment

Detailed Description

In a placebo-controlled, randomized double blind trial, the addition of evolocumab to standard care in NSTEMI patients (1) decreases LDL-C during hospitalization and at 30 days, (2) decreases vascular/plaque and myocardial inflammation as assessed by Positron Emission Tomography (PET) scanning at 30 days, and improves (3) serum markers of endothelial function at hospital discharge and at 30 days, and (4) echocardiographic assessment of left ventricular function at 30 days and six months.

This is the first PCSK9 inhibitor trial which examines these outcomes in the ACS patient population. It will provide valuable data on the extent and time course of LDL-C reduction as well as the impact of inhibition on inflammatory markers and on imaging assessment of vascular and myocardial inflammation, all of which may significantly impact important clinical outcomes in this high risk patient cohort.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Baltimore, Maryland, United States, 21136
        • Steven Paul Schulman

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Non ST segment elevation myocardial infarction
  • Troponin I >/ 5.0 ng/dL
  • Permission of attending physician

Exclusion Criteria:

  • ST elevation myocardial infarction
  • Patients requiring invasive hemodynamic support
  • Scheduled for cardiac surgery
  • Current or prior treatment with a PCSK9 antibody
  • Current participation in an intervention clinical trial
  • Female of childbearing potential who has not used acceptable method(s) of birth control for at least one month prior to screening
  • Contraindication to statin therapy
  • Subject likely not able to complete protocol related visits or procedures
  • Latex allergy
  • History of hypersensitivity to any monoclonal antibody

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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 NSTEMI patients within 24 hours, or one day, of admission.
420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
Other Names:
  • Repatha
Placebo Comparator: Placebo
Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in LDL-Cholesterol
Time Frame: 30 days
The mean percent change from baseline in LDL-C comparing placebo and evolocumab groups at 30 days
30 days
PET Imaging for inflammation
Time Frame: 30 days.
Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the myocardium, aorta and / or carotid artery between the two treatment groups.
30 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in left ventricular volume as assessed by echocardiography
Time Frame: Baseline, day 30 and 6 months
Evaluation of left ventricular volume (ml) by echocardiography
Baseline, day 30 and 6 months
Change in ejection fraction as assessed by echocardiography
Time Frame: Baseline, day 30 and 6 months
Evaluation of ejection fraction (%) by echocardiography
Baseline, day 30 and 6 months
Change in plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels (ng/ml)
Time Frame: Baseline, day 30 and 6 months
Change from baseline in PCSK9 serum levels
Baseline, day 30 and 6 months
Change in plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)
Time Frame: Baseline, day 30 and 6 months
Change from baseline in plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) (pg/ml)
Baseline, day 30 and 6 months
PET-FDG assessed vascular inflammation
Time Frame: Baseline and day 30
Target artery to background ratio endpoint [standardized uptake value] for carotid artery or aorta
Baseline and day 30
Change in New York Heart Association (NYHA) Class
Time Frame: Baseline, day 30 and 6 months
Assess NYHA class I-IV
Baseline, day 30 and 6 months
Change in high sensitivity C-reactive protein (hs-CRP) serum levels
Time Frame: Baseline, day 30 and 6 months
Change from baseline in hs-CRP serum levels (mg/L)
Baseline, day 30 and 6 months
Change in tumor necrosis factor (TNF)-alpha serum levels
Time Frame: Baseline, day 30 and 6 months
Change from baseline in TNF-alpha serum levels (pg/mL)
Baseline, day 30 and 6 months
Change in plasma levels of Interleukin 1
Time Frame: Baseline, day 30 and 6 months
Change from baseline in serum levels of Interleukin 1 (pg/mL)
Baseline, day 30 and 6 months
Change in serum levels of Interleukin 6
Time Frame: Baseline, day 30 and 6 months
Change in baseline in serum levels of Interleukin 6 (pg/mL)
Baseline, day 30 and 6 months
Change in serum levels of Interleukin 10
Time Frame: Baseline, day 30 and 6 months
Change in baseline in serum levels of Interleukin 10 (pg/mL)
Baseline, day 30 and 6 months
Change in Canadian Angina Class
Time Frame: Baseline, 30 days, 6 months
Assess Canadian Angina Classification, I-IV
Baseline, 30 days, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2018

Primary Completion (Estimated)

April 25, 2024

Study Completion (Estimated)

April 25, 2024

Study Registration Dates

First Submitted

April 10, 2018

First Submitted That Met QC Criteria

April 23, 2018

First Posted (Actual)

May 3, 2018

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 25, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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