Clinical trial NCT06791031: InclisiRan for Early Passivation of VulneRable AthEroSclerotic PlaqueS in Patients with Acute Coronary Syndromes（REPRESS）
Official title: Rationale and Design of the REPRESS Trial: InclisiRan for Early Passivation of VulneRable AthEroSclerotic PlaqueS in Patients with Acute Coronary Syndromes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2025-01-24
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this prospective, multicenter, open-label randomized controlled trial, 180 patients with ACS are randomized in a 1:1 ratio to either "inclisiran early" intensified therapy (early adding inclisiran to moderate-intensity statin therapy) group or guideline-directed medical therapy group for 12 months. Patients experience serial OCT of the non-culprit, non-flow-limiting arteries (target vessels) at baseline (culprit lesion procedure on admission) and at 12 months. The primary endpoint is the percentage of patients with vulnerable plaques in target vessels at 1 year post randomization.


Eligibility criteria: Inclusion Criteria:

* Male or female, age ≥18 years at screening
* Acute coronary syndrome who underwent PCI of the culprit lesion: acute ST-segment elevation MI with pain onset within ≤ 24 h, or non-ST segment elevation MI, or high-risk unstable angina (aggravated angina with ischemia ST-T changes in at least 2 contiguous standard electrocardiographic leads or elevation of cardiac troponin to a level not exceeding 2 times the upper limit of normal)
* Non-culprit vessel (target vessel) meets the following criteria after PCI procedure:
* Target vessel diameter \> 2.5 mm, with suitable for OCT examination
* Target vessel with angiographically estimated stenosis (diameter stenosis 30% \~ 90%) with FFR or QFR \> 0.80
* Target vessel with OCT-detected vulnerable plaques with FCT \< 75 µm plus at least two of three features (i.e., lipid arc \> 180°, MLA \< 3.5 mm2, and presence of macrophages)
* Target vessel must be native coronary arteries, vessel segment without previous PCI procedure
* 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 pilot schedule
* Life expectancy \> 1 year

Exclusion Criteria:

* 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 and bifurcation lesion
* Severe calcification or tortuosity lesions unfavorable for OCT examination
* 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
* Coronary artery anatomy that prevents complete imaging of the segment of interest (including at least 5 mm of both edges of the stenosis)
* 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 previous MI or 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 considered to be due to an acute MI) or greater
* Familial hypercholesterolaemia
* Prior (within 90 days prior to the first study visit) use of PCSK9 inhibitors alirocumab or evolocumab
* Exposure to inclisiran or any other non-monoclonal anti-PCSK9 antibodies, either as an experimental or marketed drug, within 2 years prior to the first study visit
* History of allergy to the investigational drug or its excipients, or other siRNA drugs
* Female subjects of childbearing potential, defined as all female subjects who are physiologically capable of becoming pregnant, unless such female subjects are using an effective method of contraception during administration of the study drug
* Women who are pregnant or breastfeeding or intend to become pregnant
* Comorbidities with malignancies, active infections, or major hematologic, metabolic, or endocrine disorders are judged unsuitable by the investigator
* Severe hepatic insufficiency (Child-Pugh class C)
* Current enrollment in another investigational device or drug study
* Poor adherence and unable to complete the expected follow-up

Primary outcomes:
measure: Rate of participants with vulnerable plaques in target vessels
timeFrame: At 1 year post randomization
Secondary outcomes:
measure: Change in minimum fibrous cap thickness of target vessels
timeFrame: At 1 year post randomization
measure: Change in minimum lumen area of target vessels
timeFrame: At 1 year post randomization
measure: Change in maximum lipid core arc of target vessels
timeFrame: At 1 year post randomization
measure: Change in the presence of macrophage infiltration of target vessels
timeFrame: At 1 year post randomization
measure: Change in total cholesterol
timeFrame: At 1 year post randomization
measure: Change in apolipoprotein B
timeFrame: At 1 year post randomization
measure: Change in triglycerides
timeFrame: At 1 year post randomization
measure: Change in very low-density lipoprotein cholesterol
timeFrame: At 1 year post randomization
measure: Change in low-density lipoprotein cholesterol
timeFrame: At 1 year post randomization
measure: Change in high-density lipoprotein cholesterol
timeFrame: At 1 year post randomization
measure: Rate of participants achieving prespecified LDL-C goals
timeFrame: At 1 year post randomization
measure: Number of participants with changes in the intensity of statin therapy
timeFrame: At 1 year post randomization
measure: Number of participants with adherence to lipid lowering therapy
timeFrame: At 1 year post randomization
Other outcomes:
measure: Rate of major adverse cardiovascular events (MACEs)
timeFrame: At 1 year post randomization
Locations:
Study officials:
affiliation: Department of Cardiology, West China Hospital of Sichuan University
name: Yong He
role: PRINCIPAL_INVESTIGATOR
References: