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Evolocumab in Acute Coronary Syndrome (EVACS)

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ClinicalTrials.gov Identifier: NCT03515304
Recruitment Status : Recruiting
First Posted : May 3, 2018
Last Update Posted : November 4, 2019
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
Johns Hopkins University

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 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.

Condition or disease Intervention/treatment Phase
Acute Coronary Syndrome Drug: Evolocumab Drug: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Persons performing the PET imaging, laboratory technicians are all masked.
Primary Purpose: Treatment
Official Title: Evolocumab in Acute Coronary Syndrome: A Double-Blind Randomized Placebo Controlled Study
Actual Study Start Date : May 20, 2018
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

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.
Drug: Evolocumab
420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
Other Name: Repatha

Placebo Comparator: Placebo
Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
Drug: Placebo
Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.




Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. 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

  2. Change in ejection fraction as assessed by echocardiography [ Time Frame: Baseline, day 30 and 6 months ]
    Evaluation of ejection fraction (%) by echocardiography

  3. 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

  4. 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)

  5. 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

  6. Change in New York Heart Association (NYHA) Class [ Time Frame: Baseline, day 30 and 6 months ]
    Assess NYHA class I-IV

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. Change in Canadian Angina Class [ Time Frame: Baseline, 30 days, 6 months ]
    Assess Canadian Angina Classification, I-IV



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515304


Contacts
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Contact: Steven P Schulman, MD 410-955-7378 sschulma@jhmi.edu
Contact: Thorsten M Leucker, MD, PhD 410-955-5999 tleucke1@jhmi.edu

Locations
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United States, Maryland
Steven Paul Schulman Recruiting
Baltimore, Maryland, United States, 21136
Contact: Steven P Schulman    443-956-5698    sschulma@jhmi.edu   
Principal Investigator: Steven P Schulman, MD         
Sponsors and Collaborators
Johns Hopkins University
Washington University School of Medicine
Investigators
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Principal Investigator: Thorsten M Leucker, MD, PhD Johns Hopkins University

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03515304     History of Changes
Other Study ID Numbers: IRB00156313
First Posted: May 3, 2018    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Acute Coronary Syndrome
Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs