Early Intensive Lipid-Lowering With Inclisiran for Plaque Stabilization in Acute Coronary Syndrome

NCT07799779 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: B-2607-1057-003
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, randomized, open-label clinical trial will evaluate whether an early intensive lipid-lowering strategy can improve coronary plaque stabilization in patients hospitalized with acute coronary syndrome. A total of 294 participants will be randomly assigned in a 1:1 ratio to either an early intensive treatment strategy with a high-intensity statin, ezetimibe, and inclisiran, or a guideline-based stepwise lipid-lowering strategy. Coronary plaque characteristics will be assessed using optical coherence tomography (OCT) at baseline and at 12 months. The primary outcome is the change in minimal fibrous cap thickness from baseline to 12 months. Additional assessments will include other OCT-based plaque characteristics, lipid levels, safety outcomes, and, in a subset of participants, intravascular ultrasound measurements of plaque burden.

Conditions

Acute Coronary Syndromes (ACS)

Keywords

Inclisiran; Lipid-Lowering Therapy; Optical Coherence Tomography; Fibrous Cap Thickness; Coronary Plaque Stabilization; Atherosclerotic Plaque

Outcome Measures

Primary Outcomes (1)

• Change in Minimal Fibrous Cap Thickness

  Change from baseline to 12 months in minimal fibrous cap thickness (FCT), measured by optical coherence tomography (OCT) in one prespecified representative matched non-stented coronary plaque or segment per participant.

  Baseline to 12 months

Secondary Outcomes (3)

• Change in OCT-Derived Lipid Plaque Characteristics

  Baseline to 12 months

• Change in Lipid Parameters and LDL-C Target Attainment

  Baseline to 12 months

• Changes in IVUS-Derived Plaque Burden in the IVUS Substudy

  Baseline to 12 months

Other Outcomes (1)

• Exploratory Clinical Events

  Up to 12 months

Study Arms (2)

Early Intensive Lipid-Lowering Strategy

EXPERIMENTAL

Participants will receive an early intensive lipid-lowering strategy consisting of a high-intensity statin, ezetimibe 10 mg once daily, and inclisiran 284 mg by subcutaneous injection initiated during the index hospitalization or as early as feasible. Inclisiran will be repeated at 3 months and 9 months.

Drug: Inclisiran; Drug: Atorvastatin or Rosuvastatin; Drug: Ezetimibe

Guideline-Based Stepwise Intensification Strategy

ACTIVE COMPARATOR

Participants will receive a guideline-based stepwise lipid-lowering strategy. High-intensity statin therapy will be initiated or continued during the index hospitalization. Ezetimibe will be added according to follow-up LDL-C levels, and a PCSK9 inhibitor may be considered if the LDL-C target remains unmet.

Drug: Atorvastatin or Rosuvastatin; Drug: Ezetimibe

Interventions

Inclisiran DRUG

Inclisiran sodium 284 mg/1.5 mL will be administered by subcutaneous injection in the early intensive lipid-lowering group. Inclisiran will be initiated during the index hospitalization or as early as feasible thereafter, within 2 weeks, followed by additional doses at 3 months (±2 weeks) and 9 months (±2 weeks).

Early Intensive Lipid-Lowering Strategy

Atorvastatin or Rosuvastatin DRUG

High-intensity statin therapy will consist of atorvastatin 40-80 mg orally once daily or rosuvastatin 20 mg orally once daily, or the maximally tolerated dose. High-intensity statin therapy will be initiated or continued during the index hospitalization in both treatment groups.

Early Intensive Lipid-Lowering Strategy; Guideline-Based Stepwise Intensification Strategy

Ezetimibe DRUG

Ezetimibe 10 mg will be administered orally once daily. In the early intensive lipid-lowering group, ezetimibe will be initiated during the index hospitalization. In the guideline-based stepwise intensification group, ezetimibe will be added according to follow-up LDL-C levels if the treatment target is not achieved with high-intensity statin therapy.

Early Intensive Lipid-Lowering Strategy; Guideline-Based Stepwise Intensification Strategy

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19 to 85 years.
• Hospitalization for acute coronary syndrome (UA, NSTEMI, or STEMI) with planned coronary angiography and PCI, or PCI already performed during the index hospitalization with adequate baseline OCT images obtained during the procedure that meets the study imaging analysis criteria.
• Presence of a target vessel/segment considered by the investigator to be suitable for OCT assessment at baseline and at the 12-month follow-up.
• LDL-C level at screening meeting one of the following criteria according to background lipid-lowering therapy:
• i) ≥40 mg/dL in patients receiving stable combination therapy with a statin and ezetimibe, defined as no dose change for at least 4 weeks before screening; ii) ≥55 mg/dL in patients receiving high-intensity statin therapy; iii) ≥70 mg/dL in patients receiving low- or moderate-intensity statin therapy; or iv) ≥100 mg/dL in patients not receiving stable statin therapy.
• Provision of voluntary written informed consent after receiving sufficient information regarding the study objectives, procedures, and follow-up plan.

You may not qualify if:

• Severe hepatic dysfunction, defined as AST or ALT \>3 times the upper limit of normal.
• CK \>5 times the upper limit of normal or suspected clinically significant myopathy.
• Severe renal impairment, defined as eGFR \<30 mL/min/1.73 m².
• Severe hypersensitivity to or contraindication to statins, ezetimibe, or inclisiran.
• Pregnancy, breastfeeding, or plans to become pregnant during the study period.
• Inability to undergo 12-month follow-up coronary angiography and OCT.
• Life expectancy \<1 year or, in the investigator's judgment, inappropriate participation in the study because of concerns regarding adherence or safety.

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead
• Dotter Co., Ltd.: collaborator
• Novartis Korea Ltd.: collaborator
• Hanmi Pharmaceutical co., ltd.: collaborator

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

MeSH Terms

Conditions

Acute Coronary Syndrome; Plaque, Atherosclerotic

Interventions

ALN-PCS; Atorvastatin; Rosuvastatin Calcium; Ezetimibe

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Azetidines; Azetines

Central Study Contacts

Chang-Hwan Yoon, MD, PhD

CONTACT

+82-031-787-7019; changhwanyoon@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants and investigators are aware of treatment-group assignment. However, OCT images are analyzed by an independent imaging core laboratory blinded to treatment allocation, and major clinical events are adjudicated by an independent Clinical Event Committee blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Model Details: Participants will be randomized in a 1:1 ratio to an early intensive lipid-lowering strategy or a guideline-based stepwise intensification strategy.

Study Record Dates

• First Submitted: August 28, 2026
• First Posted: September 2, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 2, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)