Early Initiation of Tafolecimab for Patients With Acute Coronary Syndromeundergoing Percutaneous Coronary Intervention in Chinese Population

Early Initiation of Tafolecimab for Patients With Acute Coronary Syndromeundergoing Percutaneous Coronary Intervention in Chinese Population (EMPACT): A Randomized Controlled Trial

For patients with ACS undergoing PCI, intensive lipid-lowering including PCSK9 monoclonal antibody should be started as soon as possible, that is, lower LDL-C level should be achieved as soon as possible. Compared with conventional lipid-lowering regimen, it is expected that the occurrence of major adverse cardiovascular events can still be reduced after drug discontinuation. Therefore, the optimization strategy of "for patients with ACS undergoing PCI, intensive lipid-lowering with PCSK9 monoclonal antibody can be started as soon as possible" is proposed.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Coronary Syndrome; Non ST Segment Elevation Acute Coronary Syndrome
• Intervention / Treatment: Drug: Tafolecimab; Drug: Statin; Drug: Cholesterol Absorption Inhibitor

Detailed Description

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide, and its incidence is increasing yearly in China, which has not yet reached the inflection point. Acute coronary syndrome (ACS) is a severe form of ASCVD, and lipid-lowering and antithrombotic therapy are the two core therapies. In the latest ESC/EAS guidelines for lipid management, for ACS patients, the target LDL-C is <1.4 mmol/L and ≥50% reduction from baseline, and specific initiatives to achieve this target are proposed, emphasizing the timing of clinical application and status of the novel lipid-lowering agent-proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9) (hereafter referred to as PCSK9 antibody). In recent years, large-scale randomized controlled trials and outcomes of PCSK9 antibodies have demonstrated that PCSK9 antibodies further reduce adverse cardiovascular events by significantly lowering LDL-C levels under the background statin (±cholesterol absorption inhibitor ) therapy. The introduction of PCSK9 antibodies allowed for the reduction of LDL-C to unprecedented levels. From the "cholesterol principle" perspective, it is theoretically reasonable to add a PCSK9 inhibitor to statins as soon as possible during hospitalization for ACS patients. Still, there is no clear evidence from large RCTs. Current evidence supports that for ACS patients, PCSK9 antibodies could be used only when LDL-C is still not up to standard based on treatment with the maximum tolerable dose of statins during the first 2-3 months. However, the immediate initiation of PCSK9 antibodies during the acute phase of ACS (before hospital discharge) has yet to be studied.

• Study Type: Interventional
• Enrollment (Estimated): 3684
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 18 to 75 years;
• clinical diagnosis with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) ;
• undergoing PCI
• baseline LDL-C 1.8 mmol/L 3.4 mmol/L note: NSTE-ACS includes non-ST-elevation myocardial infarction and unstable angina.

Exclusion Criteria:

• Severe heart failure (Killip III or IV) or cardiogenic shock;
• Previous hemorrhagic cerebrovascular disease history;
• Uncontrolled or recurrent arrhythmic events;
• poorly controlled hypertension;
• Severe hepatic and renal insufficiency (ALT/AST> 3 times upper limit of normal, eGFR<30 ml/kg/1.73m2, or ongoing dialysis) or creatine kinase elevation>5 times upper limit of normal
• malignant tumor;
• Intolerance to statins or cholesterol absorption inhibitors;
• Intolerance to injections;
• Life expectancy <1 year;
• poor compliance.

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
Experimental: experimental group; intensive lipid lowering therapy	Drug: Tafolecimab; The PCSK9 mAb in this study is defined as Tafolecimab 150mg q2w subcutaneously. For the two groups of lipid-lowering regimens, the lipid-lowering drug regimens other than PCSK9 mAb were maintained throughout the study as much as possible in accordance with the guidelines related to blood lipids, provided that no serious safety problems occurred.; Drug: Statin; Statin are based on physician decisions, but need to be routinely dosed. Examples of Medications that Meet Study Requirements: Atorvastatin 20mg Po qn, Rosuvastatin 10mg Po qn or Pitavastatin 4mg Po qn.
Active Comparator: control group; conventional lipid lowering therapy	Drug: Statin; Statin are based on physician decisions, but need to be routinely dosed. Examples of Medications that Meet Study Requirements: Atorvastatin 20mg Po qn, Rosuvastatin 10mg Po qn or Pitavastatin 4mg Po qn.; Drug: Cholesterol Absorption Inhibitor; Cholesterol absorption inhibitors (like Ezetimibe and Hybutimibe) are based on physician decisions, but need to be routinely dosed. Examples of Medications that Meet Study Requirements: Ezetimibe 10mg Po qd.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular and cerebrovascular events (MACCE)	Including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, and coronary revascularization). The coronary revascularization includes coronary intervention (PCI), coronary artery bypass grafting (CABG).	at the end of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major adverse cardiovascular events (MACEs)	Cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina, and coronary revascularization.	at the end of 6 months
Major adverse cardiovascular and cerebrovascular events (MACCE)	Including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, and coronary revascularization). The coronary revascularization includes coronary intervention (PCI), coronary artery bypass grafting (CABG).	at the end of 1 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional observed endpoint 1	Cardiovascular death	at the end of 2 years
Additional observed endpoint 2	non-fatal myocardial infarction	at the end of 2 years
Additional observed endpoint 3	non-fatal stroke	at the end of 2 years
Additional observed endpoint 4	hospitalization for unstable angina	at the end of 2 years
Additional observed endpoint 5	coronary revascularization	at the end of 2 years

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Collaborators: Innovent Biologics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

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
• Other Study ID Numbers: 2021-CXGC03-002

Drug and device information, study documents

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