Evolocumab in STEMI

Sponsor

Sejong General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT06081803

Collaborator

Samsung Medical Center (Other), National Health Insurance Service Ilsan Hospital (Other), Chonnam National University Hospital (Other), Daegu Catholic University Medical Center (Other), Inje University Ilsan Paik Hospital (Other), Catholic University of Korea Eunpyeong St. Mary's Hospital (Other)

166

Enrollment

Location

Arms

60.8

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to compare the size of myocardial infarct between evolocumab and control groups in patients with ST segment elevation myocardial infarction who undergoing primary percutaneous coronary intervention(PCI). All study participants will undergo a cardiac MRI 4 weeks after primary reperfusion. The evolocumab group will receive 420 mg before PCI via subcutaneous injection.

Condition or Disease	Intervention/Treatment	Phase
ST Elevation Myocardial Infarction	Drug: Repatha®	Phase 3

Detailed Description

The gold standard for the treatment of ST-segment elevation myocardial infarction (STEMI) is to rapidly restore myocardial blood flow through primary percutaneous coronary intervention (primary PCI) as soon as possible. While primary PCI achieves successful reperfusion of the infarct-related epicardial coronary artery in over 90% of these patients, only approximately 35% achieve ideal reperfusion to the myocardium level. This condition is termed myocardial no-reflow or microvascular obstruction (MVO). The primary pathophysiology of MVO includes severe inflammatory reactions within the ischemic vessel, distal embolization of thrombi, microthrombi formation in the microvasculature, and microvascular spasm, tissue peri-infarct edema, and intramyocardial hemorrhage. Previous studies has reported that the use of atorvastatin 80mg before PCI can reduce myocardial injury occurring during PCI in patients with acute coronary syndrome (ACS), and can improve microvascular blood flow in STEMI patients undergoing primary PCI. Furthermore, it has been reported to improve microvascular functional impairment evaluated by microvascular resistance index in non-ST-segment elevation acute coronary syndrome patients and exhibit anti-inflammatory effects. However, Two randomized trials atorvastatin 80mg did not reduce infarct size, which was primary endpoint in STEMI patients.

Recently, strong LDL cholesterol-lowering agent, PCSK9 inhibitors, have been developed and used in clinical practice, and they seem to have pleiotropic effects similar to high-intensity statins, including anti-inflammatory and antithrombotic effects. In-vitro and vivo models have shown that the introduction of human PCSK9 increases platelet aggregation in normal adult plasma and that mice without PCSK9 exhibit decreased arterial thrombosis and thrombus stability when induced . Patients with higher levels of serum PCSK9 had higher platelet reactivity after antiplatelet therapy and an increased incidence of ischemic events following coronary intervention in ACS setting. This suggests that circulating PCSK9 contributes to arterial thrombus formation, and PCSK9 inhibition may improve this. Additionally, evolocumab is known to reduce Lp(a), which is well-known for its pro-atherosclerotic and pro-inflammatory effects, by approximately 30%.

Also, Pharmaceutically, evolocumab exhibits maximum inhibitory effect against PCSK9 within just 4 hours of injection, potentially beneficial for patients with acute myocardial infarction who need a rapid effect before the infarction fully develops.

In this clinical trial, we hypothesize that administering evolocumab before primary PCI in patients with acute STEMI may reduce MVO through its antiplatelet and anti-inflammatory effects and subsequently decrease the size of the myocardial infarction.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Evolocumab group vs control groupEvolocumab group vs control group

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effect of Evolocumab on Infarct Size in Patients With ST-segment Elevation Myocardial Infarction; Prospective, Randomized, Open Label, Controlled Trial

Actual Study Start Date :

Dec 5, 2020

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Evolocumab group Evolocumab 420mg subcutaneous injection before primary PCI	Drug: Repatha® Repatha® 140mg x 3 pens subcutaneous injection
No Intervention: Control group without Evolocumab 420mg before primary PCI

Arm

Intervention/Treatment

Experimental: Evolocumab group

Evolocumab 420mg subcutaneous injection before primary PCI

Drug: Repatha®

Repatha® 140mg x 3 pens subcutaneous injection

No Intervention: Control group

without Evolocumab 420mg before primary PCI

Outcome Measures

Primary Outcome Measures

Myocardial infarct size [1 month after primary reperfusion]
assessed by cardiac MRI

Secondary Outcome Measures

The incidence of MVO [1 month after primary reperfusion]
assessed by cardiac MRI

Other Outcome Measures

ST segment resolution [1 hour after primary reperfusion]
assessed by 12-leads ECG
Area under the curve of enzymatic infarct size [within 48 hours after primary reperfusion]
Myocardial blush grade [Immediate after primary reperfusion]
assessed by coronary angiography
Corrected TIMI frame count [Immediate after primary reperfusion]
assessed by coronary angiography
TIMI myocardial perfusion grade [Immediate after primary reperfusion]
assessed by coronary angiography
The change of LDL-Cholesterol from baseline [1 month after primary reperfusion]
The change of Lipoprotein (a) from baseline [1 month after primary reperfusion]
Platelet reactivity on treatment [1 month after primary reperfusion]
Assessed by Verifynow
Hs-CRP level [1 month after primary reperfusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Typical ischemic chest pain persists for more than 30 minutes
An elevation of an ST segment greater than 1 mm in two consecutive leads or new-onset left bundle branch block
Presenting more than 12 hours after the onset of symptoms