Evolocumab in Acute Coronary Syndrome (EVACS)

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Acute Coronary Syndrome

Treatments: Drug: Evolocumab; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03515304

IRB00156313

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 25 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Evolocumab

Experimental group

Description:

420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.

Treatment:

Drug: Evolocumab

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo