Preventive Intervention Value of Inclisiran Combined With DCB in Vulnerable Coronary Atherosclerotic Plaques

Preventive Intervention Value of Inclisiran Combined With Drug-Coated Balloons in Vulnerable Coronary Atherosclerotic Plaques

The PASSIVATE-CAP study is an investigator-initiated, prospective, randomized, multicenter, open-label superiority trial focusing on acute coronary syndrome (ACS) patients with nonflow-limiting vulnerable plaques in nonculprit vessels. In this study, eligible patients were randomized at a 1:1 ratio into two groups: patients who received guideline-directed medical therapy (GDMT) and patients who received GDMT combined with a drug-coated balloon (DCB). In this study, the use of PCSK9 inhibitors was limited to inclisiran. The primary endpoint was the minimal lumen area of the target lesion 1 year after randomization. The secondary endpoints encompass a range of factors, including the proportion of patients with vulnerable plaques in the target vessel, fibrous cap thickness, lipid core arc of the target lesion, minimal lumen area of the target vessel, and extent of LDL-C reduction in patients treated with inclisiran.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Procedure: GDMT+DCB

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Age ≥ 18 years Diagnosis of ACS with the intention to undergo ICA There exists a nonculprit lesion characterized by a single diameter stenosis greater than 50% in the major coronary artery segments (with diameters ranging from 2.75 to 4 mm).

QFR value > 0.8 The OCT examination suggests vulnerable plaques with a fibrous cap thickness of < 65 µm, along with at least two of the other three OCT criteria Minimum lumen area <3.5 mm² Lipid core angle >180° Presence of macrophages lesion length ≤30 mm Provide informed consent Life expectancy greater than 1 year

Exclusion Criteria:

Patients with three or more target lesions or with two target lesions in the same coronary artery left main stem lesions Ostial lesions Thrombotic lesions Severe calcification or angulated lesions True bifurcation lesions requiring stent implantation Advanced heart failure (NYHA III-IV) Ischemic stroke in the past 6 months or any history of cerebral hemorrhage at any time Severe valve disease or valve disease that may require surgical or percutaneous valve replacement Coronary artery anatomy obstructs the complete imaging of the segment of interest (including at least 5 mm beyond the narrow ends).

Diffuse coronary artery disease or the presence of ≥1 untreated nonculprit lesion (nonculprit blood flow-restricting lesion planned for staged PCI).

History of myocardial infarction, CABG, or PCI Coronary artery anatomy not suitable for PCI The potential comorbidity that may impact the completion of the trial process. The planned major surgery requires discontinuation of DAPT. History of PCSK9 inhibitor (such as evolocumab or alirocumab) use within 90 days prior to the first study visit.

Exposed to Inclisiran or any other non-PCSK9 monoclonal antibody targeted treatment within the 2 years preceding the initial study visit, whether as an investigational drug or a marketed medication.

History of allergy to the investigational drug, its excipients, or other siRNA drugs Females of childbearing potential, defined as all female subjects physiologically capable of becoming pregnant, unless they are using effective contraception during the administration of the investigational drug

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: GDMT
Experimental: GDMT+DCB	Procedure: GDMT+DCB; Preventive Intervention on Eligible Vulnerable Plaques Using DCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum luminal area	Minimum luminal cross-sectional area of the target lesion measured 1 year after randomization.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients with vulnerable plaques in the target vessel	proportion of patients with vulnerable plaques in the target vessel	1 year
fibrous cap thickness	Fibrous cap thickness	1 year
lipid core arc	The lipid core arc as visualized on optical coherence tomography (OCT) refers to the angular extent and characteristics of the lipid-rich region within an atherosclerotic plaque. On cross-sectional OCT imaging, the lipid core appears as an area with high backscattering and high signal attenuation, distinguishing it from the surrounding fibrous or calcified plaque components. The key features of the lipid core arc include the arc angle (the angular extent of the lipid core in degrees), the arc thickness (the maximal radial thickness of the lipid core), and the arc location (the position of the lipid core relative to the lumen and other plaque components).	1 year
Changes in LDL-C	The degree of changes in patients' LDL-C (low-density lipoprotein cholesterol) levels before and after treatment	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target vessel failure	A composite endpoint event encompassing cardiac death, target vessel myocardial infarction, and ischemia-driven target vessel revascularization.	1 year

Collaborators and Investigators

• Sponsor: Yong He

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 2, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Acute Coronary Syndrome; Plaque, Atherosclerotic
• Other Study ID Numbers: WestChinaH-CVD-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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