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| Name | Class |
|---|---|
| Amgen | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Evolocumab | Experimental | 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
|
| Placebo | Placebo Comparator | Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab | Drug | 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in LDL-Cholesterol | Baseline to 30 days | |
| Change From Baseline in Target to Background Ratio Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scans | PET Imaging for Inflammation: Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the myocardium. | Baseline to 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Left Ventricular Volume as Assessed by Echocardiography | Evaluation of left ventricular volume (ml) by echocardiography | Baseline, day 30 and 6 months |
| Ejection Fraction as Assessed by Echocardiography |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thorsten M Leucker, MD, PhD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Steven Paul Schulman | Baltimore | Maryland | 21136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35314069 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Evolocumab | 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. Evolocumab: 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
| FG001 | Placebo | Placebo 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | placebo group |
| BG001 | Evolocumab | evolocumab group |
| BG002 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in LDL-Cholesterol | Participants with data collected | Posted | Median | Inter-Quartile Range | percent change | Baseline to 30 days |
|
from enrollment through 30-day follow-up
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Evolocumab | 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. Evolocumab: 420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury requiring intermittent hemodialysis | Renal and urinary disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Thorsten Leucker | Johns Hopkins University - Baltimore, MD | 4105020469 | tleucke1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 5, 2020 | Sep 4, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D054058 | Acute Coronary Syndrome |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C577155 | evolocumab |
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Double-blind, placebo controlled trial
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Persons performing the PET imaging, laboratory technicians are all masked.
| Placebo | Drug | Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission. |
|
Evaluation of ejection fraction (%) by echocardiography
| Baseline, day 30 and 6 months |
| Plasma Proprotein Convertase Subtilisin Kexin-9 (PCSK9) Levels (ng/ml) | Change from baseline in PCSK9 serum levels | Baseline, day 30 and 6 months |
| PET-FDG Assessed Vascular Inflammation as Assessed by Standardized Uptake Value (SUV) | Target artery to background ratio endpoint (standardized uptake value) for left carotid artery | Baseline to day 30 |
| High Sensitivity C-reactive Protein (Hs-CRP) Serum Levels | hs-CRP serum levels (mg/L) | Baseline, day 30 and 6 months |
| Change in Serum Levels of Interleukin 6 | Change in baseline in serum levels of Interleukin 6 (pg/mL) | Baseline, day 30 and 6 months |
| Serum Levels of Interleukin 10 | Serum levels of Interleukin 10 (pg/mL) | Baseline, day 30 and 6 months |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Primary | Change From Baseline in Target to Background Ratio Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scans | PET Imaging for Inflammation: Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the myocardium. | Participants with PET data collected and adequate image quality for analysis | Posted | Mean | Standard Deviation | ratio | Baseline to 30 days |
|
|
|
| Secondary | Left Ventricular Volume as Assessed by Echocardiography | Evaluation of left ventricular volume (ml) by echocardiography | Participants with data collected and evaluable images | Posted | Mean | Standard Deviation | ml | Baseline, day 30 and 6 months |
|
|
|
| Secondary | Ejection Fraction as Assessed by Echocardiography | Evaluation of ejection fraction (%) by echocardiography | Participants with data collected and evaluable images | Posted | Mean | Standard Deviation | percent | Baseline, day 30 and 6 months |
|
|
|
| Secondary | Plasma Proprotein Convertase Subtilisin Kexin-9 (PCSK9) Levels (ng/ml) | Change from baseline in PCSK9 serum levels | Participants with data collected | Posted | Mean | Standard Deviation | ng/ml | Baseline, day 30 and 6 months |
|
|
|
| Secondary | PET-FDG Assessed Vascular Inflammation as Assessed by Standardized Uptake Value (SUV) | Target artery to background ratio endpoint (standardized uptake value) for left carotid artery | Participants with PET data collected and adequate image quality for analysis | Posted | Mean | Standard Deviation | SUV | Baseline to day 30 |
|
|
|
|
| Secondary | High Sensitivity C-reactive Protein (Hs-CRP) Serum Levels | hs-CRP serum levels (mg/L) | Participants with data collected | Posted | Mean | Standard Deviation | mg/L | 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) | Participants with data collected | Posted | Mean | Standard Deviation | pg/ml | Baseline, day 30 and 6 months |
|
|
|
| Secondary | Serum Levels of Interleukin 10 | Serum levels of Interleukin 10 (pg/mL) | Participants with data collected | Posted | Mean | Standard Deviation | pg/ml | Baseline, day 30 and 6 months |
|
|
|
| 0 |
| 30 |
| 2 |
| 30 |
| 13 |
| 30 |
| EG001 | Placebo | Placebo 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. | 0 | 30 | 6 | 30 | 6 | 30 |
| Gastrointestinal bleed | Gastrointestinal disorders | Non-systematic Assessment |
|
| Recurrent non-ST elevation myocardial infarction | Cardiac disorders | Non-systematic Assessment |
|
| Transient myocardial ischemia prompting hospitalization | Cardiac disorders | Non-systematic Assessment |
|
| Hospitalization for planned vascular surgery | Vascular disorders | Non-systematic Assessment |
|
| Hospitalization for neck pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Transient ischemic attack, slurred speech | Nervous system disorders | Non-systematic Assessment |
|
| Retinal artery occlusion | Eye disorders | Non-systematic Assessment |
|
| Pre-syncope | Nervous system disorders | Non-systematic Assessment |
|
| Ecchymosis injection site | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Post-infarction pericarditis | Cardiac disorders | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | Non-systematic Assessment |
|
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| Day 30 Systolic Volume months |
|
|
| 6 month Systolic Volume |
|
|
| Baseline Diastolic Volume |
|
|
| Day 30 Diastolic Volume |
|
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| 6 month Diastolic Volume |
|
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| Day 30 Ejection Fraction |
|
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| 6 month Ejection Fraction |
|
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| Day 30 PCSK9 serum level |
|
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| 6 months PCSK9 serum level |
|
|
| Day 30 hs-CRP |
|
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| 6 month hs-CRP |
|
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| Day 30 Interleukin 6 |
|
|
| 6 month Interleukin 6 |
|
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| Day 30 Interleukin 10 |
|
|
| 6 month Interleukin 10 |
|
|