Evolocumab in Acute Coronary Syndrome

Acute Coronary Syndrome Clinical Trial

— EVACS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03515304
• Other study ID #: IRB00156313
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 20, 2018
• Est. completion date: October 25, 2024

Study information

• Verified date: May 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: October 25, 2024
• Est. primary completion date: October 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Steven Paul Schulman	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	Amgen, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

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