PCSK9 inhibitoRs for Early Passivation of coRonary athEroSclerotic plaqueS in Acute Coronary Syndromes (REPRESS)

NCT06791031 | Not Yet Recruiting DMC

• 1 other identifier: WestChinaH-CVD-009
• Study Type: interventional
• Target: 212
• Locations: 0 countries
• Sites: N/A

Brief Summary

In this prospective, multicenter, open-label trial, 212 ACS patients will be randomized 1:1 to either the "PCSK9i early" intensified therapy group (initial addition of PCSK9i to moderate-intensity statin) or the guideline-directed medical therapy group for 6 months. Serial OCT imaging of non-culprit arteries (20-70% stenosis) is performed at baseline and 6 months. The primary endpoint is the absolute change in minimum fibrous cap thickness at 6 months, and secondary endpoints including changes in lumen area, lipid arc, macrophage infiltration, LDL-C reduction, and target LDL-C achievement.

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Absolute change in the minimum fibrous cap thickness of target lesions

  Absolute change in the minimum fibrous cap thickness of target lesions from baseline to 6 months.

  At 6 months post randomization

Secondary Outcomes (15)

• Percent change in minimum fibrous cap thickness of target vessels

  At 6 months post randomization

• Absolute change in mean minimum fibrous cap thickness across target vessels

  At 6 months post randomization

• Absolute changes in minimum lumen area of target vessels

  At 6 months post randomization

• Absolute changes in maximum lipid arc of target vessels

  At 6 months post randomization

• Presence of macrophage infiltration in target vessels

  At 6 months post randomization

Other Outcomes (8)

• Incidence of major adverse cardiovascular events (MACEs)

  At 6 months and 12 months post randomization

• Incidence of bleeding events

  At 6 months and 12 months post randomization

• Change in high-sensitivity C-reactive protein

  At 3 months and 6 months post randomization

Study Arms (2)

"PCSK9i early" intensified therapy group

EXPERIMENTAL

Initial addition of PCSK9i to moderate-intensity statin

Drug: PCSK9 inhibitor (PCSK9i)

Guideline-directed medical therapy group

NO INTERVENTION

Stepwise lipid-lowering strategies based on the 2025 American College of Cardiology/American Heart Association guidelines for ACS, Chinese Lipid Management Guidelines (2023), and Expert Consensus on Clinical Pathways for Lipid Management in Chinese Patients with ACS.

Interventions

PCSK9 inhibitor (PCSK9i) DRUG

Patients randomized to the "PCSK9i early" intensified therapy group will receive initial treatment with a PCSK9 inhibitor-either evolocumab 140 mg or alirocumab 75 mg, both administered subcutaneously every two weeks with the initial dose given during hospitalization and subsequent doses self-administered at home-or inclisiran sodium 300 mg (equivalent to 284 mg inclisiran), administered by healthcare professionals at baseline and again at the 3-month study visit. All patients will receive moderate-intensity statin, including atorvastatin 20 mg or rosuvastatin 10 mg. The intervention will be initiated during hospitalization for the index ACS event, within 24 hours of randomization, irrespective of baseline LDL-C levels or prior statin use.

"PCSK9i early" intensified therapy group

Eligibility Criteria

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

You may qualify if:

• Male or female, age ≥ 18 years at screening
• Acute coronary syndrome who underwent PCI of the culprit lesions.
• Non-culprit vessel (target vessel) meets the following criteria after culprit vessel PCI:
• Target vessel diameter \> 2.5 mm, suitable for OCT examination
• Target vessel with angiographically estimated stenosis (diameter stenosis 20-70%)
• Target vessel must be native coronary arteries, vessel segment without previous PCI
• Target vessel cannot be a venous or arterial bridge vessel
• Ability to cooperate the requirements of the study and to offer written informed consent
• Willingness to complete follow-up visits and examinations as required by the schedule
• Life expectancy \> 1 year

You may not qualify if:

• Left main disease of non-culprit artery, defined as ≥ 50% reduction in lumen diameter of the left main coronary artery via angiographic visual estimation
• Thrombotic target lesion, severe calcification or tortuosity lesions unfavorable for OCT examination
• Coronary artery anatomy that prevents complete imaging of the segment of interest (including at least 5 mm of both edges of the stenosis)
• True bifurcation lesions requiring stenting
• TIMI flow \< 2 of the culprit-related arteries after PCI
• Unstable clinical status (cardiogenic shock, hemodynamic or electrical instability)
• Advanced heart failure (New York cardiac class III-IV)
• Ischaemic stroke within the past 6 months or cerebral haemorrhage at any time in the past
• Severe valvular disease or valvular disease that may require surgery or percutaneous valve replacement
• Diffuse coronary artery lesions or the presence of ≥ 1 untreated non-culprit lesion (non-culprit flow-restricting lesion planned for near-term, phase II PCI)
• Target vessel with coronary artery bypass grafting or PCI
• Planned major surgery requiring interruption of dual-antiplatelet therapy
• Statin intolerance and patients unsuitable for statin therapy with alanine aminotransferase greater than 3 times the upper limit of normal or creatine kinase greater than 3 times the upper limit of normal (not attribute to an acute MI) or greater
• Familial hypercholesterolaemia
• Prior (within 180 days prior to the first study visit) exposure to PCSK9i, either as an experimental or marketed drug

Sponsors & Collaborators

• West China Hospital: lead

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Yong He

  Department of Cardiology, West China Hospital of Sichuan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong He

CONTACT

18980602038; heyongmd@wchscu.cn

Zhongxiu Chen

CONTACT

18030708238; czxlfb1988@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 11, 2025
• First Posted: January 24, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: November 28, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share