EVACS: Evolocumab in Acute Coronary Syndrome
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Evolocumab 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
Drug: Evolocumab
420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
Other Names:
|
| Placebo Comparator: Placebo Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
Drug: Placebo
Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
|
Outcome Measures
Primary Outcome Measures
- Change in LDL-Cholesterol [30 days]
The mean percent change from baseline in LDL-C comparing placebo and evolocumab groups at 30 days
- PET Imaging for inflammation [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.
Secondary Outcome Measures
- Change in left ventricular volume as assessed by echocardiography [Baseline, day 30 and 6 months]
Evaluation of left ventricular volume (ml) by echocardiography
- Change in ejection fraction as assessed by echocardiography [Baseline, day 30 and 6 months]
Evaluation of ejection fraction (%) by echocardiography
- Change in plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels (ng/ml) [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) [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 [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 [Baseline, day 30 and 6 months]
Assess NYHA class I-IV
- Change in high sensitivity C-reactive protein (hs-CRP) serum levels [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 [Baseline, day 30 and 6 months]
Change from baseline in TNF-alpha serum levels (pg/mL)
- Change in plasma levels of Interleukin 1 [Baseline, day 30 and 6 months]
Change from baseline in serum levels of Interleukin 1 (pg/mL)
- Change in serum levels of Interleukin 6 [Baseline, day 30 and 6 months]
Change in baseline in serum levels of Interleukin 6 (pg/mL)
- Change in serum levels of Interleukin 10 [Baseline, day 30 and 6 months]
Change in baseline in serum levels of Interleukin 10 (pg/mL)
- Change in Canadian Angina Class [Baseline, 30 days, 6 months]
Assess Canadian Angina Classification, I-IV
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Steven Paul Schulman | Baltimore | Maryland | United States | 21136 |
Sponsors and Collaborators
- Johns Hopkins University
- Washington University School of Medicine
- Amgen
Investigators
- Principal Investigator: Thorsten M Leucker, MD, PhD, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00156313