PCSK9 Inhibitor on ACS Patients With Multivessel Disease and Relatively Low LDL-C Level in Chinese Population

Effect of PCSK9 Inhibitor on Acute Coronary Syndrome Patients With Multivessel Disease and Relatively Low LDL-C Level in Chinese Population (CHOICE Study)

The study is an open-label, multicenter, and randomized study. The objective of this study is to demonstrate the effect of PCSK9 inhibitor on ACS patients with multivessel disease and relatively low LDL-C levels or LDL-C levels lower than the recommended target.

The primary outcome was the rate of major adverse cardiac events (CV death, non-fatal myocardial infarction, documented unstable angina that requires admission into a hospital, all coronary revascularization with either PCI or CABG occurring at least 30 days after randomization, Non-fatal stroke) at 1 year. The secondary efficacy endpoints were individual components of the major adverse cardiac events, all cause death, and the percent change in LDL-C, Apo B, HDL-C, Lp(a) after treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Repatha or Praluent

• Study Type: Interventional
• Enrollment (Anticipated): 1360
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 40-85 years age;
• Recent hospitalization for acute coronary syndrome
• LDL-C ≤70 mg/dL (≤1.8 mmol/L) in patients who have been receiving stable treatment with moderate- or high-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks) or, LDL-C ≤90 mg/dL (≤2.3 mmol/L) in patients who have been receiving stable treatment with low-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks), or LDL-C≤125 mg/dL (≤3.2 mmol/L) in patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment;
• Multivessel disease, defined as ≥50% reduction in lumen diameter of at least three major epicardial coronary arteries by angiographic visual estimation or in major branches of one or more of these arteries, irrespective of the localization (proximal 50mm or more distal localization) of the obstructive lesions
• Patients with written informed consent.

Exclusion Criteria:

• Unstable clinical status (hemodynamic or electrical instability); Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening;
• Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m2;
• Active liver disease or hepatic dysfunction, either reported in patient medical record or defined by asparate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3x the upper limit of normal;
• Patients who previously received evolocumab or other PCSK9 inhibitor;
• Treatment with systemic steroids or systemic cyclosporine in the past 3 months systemic cyclosporine, systemic steroids (eg. intravenous, intramuscular or per os);
• Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator;
• Patients who will not be available for study-required procedures in the judgment of the Investigator;
• Current enrollment in another investigational device or drug study;
• Active malignancy requiring treatment;
• Intolerance of or allergy to statin or PCSK9 inhibitor;
• pregnancy, giving birth within the last 90 days, or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard of care: management as recommended in ESC/EAS 2019 guidelines, within reimbursement criteria
Experimental: treatment; On top of Standard of care, Evolocumab (Repatha®) 140 mg or Alirocumab(Praluent) 75mg every two weeks: first subcutaneous injection at the time of randomization, followings during 12 months.	Drug: Repatha or Praluent; Evolocumab (Repatha®) 140 mg or Alirocumab (Praluent) 75mg every two weeks, first subcutaneous injection at the time of randomization, followings during 12 months; Other Names: Evolocumab or Alirocumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint	The primary endpoint in the CHOICE study was the rate of major adverse cardiac events at 1 year. The definition of major adverse cardiac events was a composite of: CV death; Major coronary events 1) non-fatal myocardial infarction [MI]; 2)documented unstable angina that requires admission into a hospital; 3)all coronary revascularization with either PCI or CABG occurring at least 30 days after randomization); Non-fatal stroke	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoint	The secondary efficacy endpoints were individual components of the major adverse cardiac events, all cause death, and the percent change in LDL-C, Apo B, HDL-C, Lp(a) at 1 year.	12 months
Secondary Endpoint	the percent change in LDL-C, Apo B, HDL-C, Lp(a) at 1 year.	12 months

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: August 29, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• 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: CHOICE202101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No