Evolocumab in Acute Coronary Syndrome (EVACS)

• ClinicalTrials.gov Identifier: NCT03515304
• Recruitment Status: Recruiting
• First Posted: May 3, 2018
• Last Update Posted: December 17, 2020
• Sponsor: Johns Hopkins University
• Collaborators: Washington University School of Medicine; Amgen
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: April 10, 2018
• First Posted Date: May 3, 2018
• Last Update Posted Date: December 17, 2020
• Actual Study Start Date: May 20, 2018
• Estimated Primary Completion Date: February 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Evolocumab in Acute Coronary Syndrome
• Official Title: 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: Interventional
• Study Phase: Phase 2

Study Design

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: Acute Coronary Syndrome

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 23, 2018): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 1, 2021
• Estimated Primary Completion Date: February 1, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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: United States

Administrative Information

• NCT Number: NCT03515304
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Johns Hopkins University
• Study Sponsor: Johns Hopkins University

Collaborators

• Washington University School of Medicine
• Amgen

Investigators

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

• PRS Account: Johns Hopkins University
• Verification Date: December 2020