Evolocumab in STEMI

ST Elevation Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06081803
• Other study ID #: EVO-STEMI_version 4.1
• Status: Recruiting
• Phase: Phase 3
• Start date: December 5, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Sejong General Hospital
• Contact: Hyun-Jong Lee, MD, PhD
• Phone: 82-10-6217-9315
• Email: untouchables00[@]hanmail.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 166
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Exclusion Criteria:

• Previous history of myocardial infarction

• Previous history of coronary bypass surgery

• Cardiogenic shock that lasts more than 10 minutes or cardiac arrest

• Occlusion of the left main coronary artery

• Pregnant or have a plan of pregnancy

• Serum creatinine level is >2.5mg/dL or dialysis is required

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Repatha®
Repatha® 140mg x 3 pens subcutaneous injection

Locations

Country	Name	City	State
Korea, Republic of	Sejong General Hospital	Bucheon

Sponsors (7)

Lead Sponsor	Collaborator
Sejong General Hospital	Catholic University of Korea Eunpyeong St. Mary's Hospital, Chonnam National University Hospital, Daegu Catholic University Medical Center, Inje University Ilsan Paik Hospital, National Health Insurance Service Ilsan Hospital, Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ST segment resolution	assessed by 12-leads ECG	1 hour after primary reperfusion
Other	Area under the curve of enzymatic infarct size		within 48 hours after primary reperfusion
Other	Myocardial blush grade	assessed by coronary angiography	Immediate after primary reperfusion
Other	Corrected TIMI frame count	assessed by coronary angiography	Immediate after primary reperfusion
Other	TIMI myocardial perfusion grade	assessed by coronary angiography	Immediate after primary reperfusion
Other	The change of LDL-Cholesterol from baseline		1 month after primary reperfusion
Other	The change of Lipoprotein (a) from baseline		1 month after primary reperfusion
Other	Platelet reactivity on treatment	Assessed by Verifynow	1 month after primary reperfusion
Other	Hs-CRP level		1 month after primary reperfusion
Primary	Myocardial infarct size	assessed by cardiac MRI	1 month after primary reperfusion
Secondary	The incidence of MVO	assessed by cardiac MRI	1 month after primary reperfusion