Clinical trial NCT03515304: Evolocumab in Acute Coronary Syndrome
Official title: Evolocumab in Acute Coronary Syndrome: A Double-Blind Randomized Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Coronary Syndrome
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2018-05-03
Enrollment: 60
Sex: ALL
Minimum age (years): 25
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo controlled trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in LDL-Cholesterol
timeFrame: 30 days
measure: PET Imaging for inflammation
timeFrame: 30 days.
Secondary outcomes:
measure: Change in left ventricular volume as assessed by echocardiography
timeFrame: Baseline, day 30 and 6 months
measure: Change in ejection fraction as assessed by echocardiography
timeFrame: Baseline, day 30 and 6 months
measure: Change in plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels (ng/ml)
timeFrame: Baseline, day 30 and 6 months
measure: Change in plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)
timeFrame: Baseline, day 30 and 6 months
measure: PET-FDG assessed vascular inflammation
timeFrame: Baseline and day 30
measure: Change in New York Heart Association (NYHA) Class
timeFrame: Baseline, day 30 and 6 months
measure: Change in high sensitivity C-reactive protein (hs-CRP) serum levels
timeFrame: Baseline, day 30 and 6 months
measure: Change in tumor necrosis factor (TNF)-alpha serum levels
timeFrame: Baseline, day 30 and 6 months
measure: Change in plasma levels of Interleukin 1
timeFrame: Baseline, day 30 and 6 months
measure: Change in serum levels of Interleukin 6
timeFrame: Baseline, day 30 and 6 months
measure: Change in serum levels of Interleukin 10
timeFrame: Baseline, day 30 and 6 months
measure: Change in Canadian Angina Class
timeFrame: Baseline, 30 days, 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Steven Paul Schulman
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Thorsten M Leucker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vavuranakis MA, Jones SR, Ziogos E, Blaha MJ, Williams MS, Foran P, Schindler TH, Lai S, Schulman SP, Gerstenblith G, Leucker TM. The Trajectory of Lipoprotein(a) During the Peri- and Early Postinfarction Period and the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition. Am J Cardiol. 2022 May 15;171:1-6. doi: 10.1016/j.amjcard.2022.01.058. Epub 2022 Mar 21.