Effect of Evolocumab Added to Moderate-Intensity Statin Therapy on LDL-C Lowering and Cardiovascular Adverse Events in Patients With Acute Coronary Syndrome (EMSIACS)

The study is an open-label, multicenter, and randomized study(five hospitals).The purpose of this study is to assess the differences in the effects of the evolocumab added to moderate-intensity statin therapy and the moderate-intensity statin only therapy on the regulation of LDL-C levels in patients with acute phase acute coronary syndrome after four weeks of treatment. The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12 weeks and 1 year of treatment.

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndrome; Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor
• Intervention / Treatment: Drug: Evolocumab

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing Gao, PHD; Phone Number: +86-13820156072; Email: gaojing2088@163.com

Study Locations

• China
  • Tianjin, China, 300222
    • Recruiting
    • Tianjin Chest Hospital,
    • Contact: JING GAO, PH.D; Phone Number: 13820156072; Email: gaojing2088@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recent hospitalization for acute coronary syndrome: Complies with the diagnostic criteria for acute coronary syndrome (non-ST-segment elevation myocardial infarction, acute ST-segment elevation myocardial infarction, and unstable angina within 72 hours of onset)

• LDL-C level (meet one of the following conditions):

  1. Prior to the study, patients who received intensive statins for more than 4 weeks (the same dose of statin therapy has been sustained for the past four weeks) with LDL-C levels ≥70 mg/dL (≥1.8 mmol/L) or non-HDL-C ≥100 mg /dL (≥2.6mmol/L) are included in the study;
  2. Prior to the study, patients who received moderate-intensity statin therapy for more than 4 weeks (the same dose of statin therapy has been sustained for the past four weeks) with LDL-C levels ≥90 mg/dL (≥2.3 mmol/L) or non-HDL-C≥ 120mg/dL (≥3.1mmol/L) are included in the study;
  3. Prior to the study, patients who do not receive statin therapy or who do not continue to receive statin with LDL-C ≥ 125 mg/dL (≥ 3.2 mmol/L) or non-HDL-C ≥ 155 mg/dL (≥ 4.0 mmol/L).
• Being able to understand research requirements and sign informed consent

Exclusion Criteria:

• Unstable clinical status (hemodynamics or ECG instability)
• Uncontrolled arrhythmia, defined as recurrent or symptomatic ventricular tachycardia and atrial fibrillation with rapid ventricular reaction that the drug cannot control within three months prior to screening
• Severe renal insufficiency, defined as estimated glomerular filtration rate<30ml/min/1.73m2
• Active liver disease or liver dysfunction, whether it is on the patient's medical record or defined as an increase in alanine aminotransferase or aspartate aminotransferase more than 3 times above the upper limit of normal
• Records on statin or rosuvastatin (any dose) intolerance or other statin intolerance
• Known allergies to contrast agents, heparin, aspirin, ticagrelor or clopidogrel
• Known allergies to the supplements required for the use of the drug
• Patients who have been treated with evolocumab or other PCSK9 inhibitors
• Received cholesterol ester transfer protein inhibitors treatment 12 months prior to screening
• Received systemic steroid or cyclosporine treatment in the past 3 months
• Known infections, hemorrhages, metabolic or endocrine disorders as determined by the researchers
• Patients who have been included in other studies
• Patients with active malignant tumor in need of treatment
• Women with fertility (age <50 years, menstruation in the past 12 months), did not receive tubal ligation, oophorectomy or hysterectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the evolocumab plus statin therapy; Patients with ACS are treated with atorvastatin (20mg) daily and evolocumab (140 mg) every two weeks throughout the study period	Drug: Evolocumab; Patients were randomly assigned of the ratio of 1:1 using a computer-generated random number and divided into two treatment groups: the statin alone therapy and the evolocumab plus statin therapy.
No Intervention: the statin alone therapy; Patients with ACS are treated with atorvastatin (20mg) daily throughout the study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change in LDL-C	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major cardiovascular adverse events	Coronary heart disease death，nonfatal myocardial infarction，hospitalization for unstable angina，unplanned coronary revascularization, and stroke	4 weeks and 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean percentage change from baseline in LDL-C levels		within 1 year
The proportion of patients with LDL-C <70 mg/dL during treatment		week 4 and week 12
the quality of life of patients	using EQ-5D-3L questionnaire score to assess the quality of life	week 12 and week 48
The effect of evolocumab on platelet function based on the area under curve	using Col/ADP test to evaluate platelet function	from baseline to 72 hours and baseline to week 4
the effect of evolocumab on the percentage change of inflammatory markers (high-sensitivity C-reactive protein)		from baseline to week 48

Collaborators and Investigators

• Sponsor: Tianjin Chest Hospital

Publications and helpful links

General Publications

• Gao J, Liu JY, Lu PJ, Xiao JY, Gao MD, Li CP, Cui Z, Liu Y. Effects of Evolocumab Added to Moderate-Intensity Statin Therapy in Chinese Patients With Acute Coronary Syndrome: The EMSIACS Trial Study Protocol. Front Physiol. 2021 Nov 23;12:750872. doi: 10.3389/fphys.2021.750872. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: September 21, 2019
• First Submitted That Met QC Criteria: September 21, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 20, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Acute Coronary Syndrome; Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor; Lipid-lowering Drug; Major Cardiovascular Adverse Events
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: EMSIACS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes