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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 : January 2, 2020
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE April 10, 2018
First Posted Date  ICMJE May 3, 2018
Last Update Posted Date January 2, 2020
Actual Study Start Date  ICMJE May 20, 2018
Estimated Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2019)
  • 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
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2018)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2019)
  • 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
  • Change in ejection fraction as assessed by echocardiography [ Time Frame: Baseline, day 30 and 6 months ]
    Evaluation of ejection fraction (%) by echocardiography
  • 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
  • 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)
  • 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
  • Change in New York Heart Association (NYHA) Class [ Time Frame: Baseline, day 30 and 6 months ]
    Assess NYHA class I-IV
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Change in Canadian Angina Class [ Time Frame: Baseline, 30 days, 6 months ]
    Assess Canadian Angina Classification, I-IV
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2018)
PET Imaging for inflammation [ Time Frame: 30 days. ]
Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the aorta and / or carotid artery between the two treatment groups.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evolocumab in Acute Coronary Syndrome
Official Title  ICMJE Evolocumab in Acute Coronary Syndrome: A Double-Blind Randomized Placebo Controlled Study
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Acute Coronary Syndrome
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
Study Arms  ICMJE
  • Experimental: Evolocumab
    420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
    Intervention: Drug: Evolocumab
  • Placebo Comparator: Placebo
    Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2021
Estimated Primary Completion Date February 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Steven P Schulman, MD 410-955-7378 sschulma@jhmi.edu
Contact: Thorsten M Leucker, MD, PhD 410-955-5999 tleucke1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03515304
Other Study ID Numbers  ICMJE IRB00156313
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Washington University School of Medicine
Investigators  ICMJE
Principal Investigator: Thorsten M Leucker, MD, PhD Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP