Management of LDL-cholesterol With Inclisiran + Usual Care Compared to Usual Care Alone in Participants With a Recent Acute Coronary Syndrome

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to study the effectiveness of implementation of a systematic LDL-C management pathway including treatment with inclisiran in participants who have experienced a recent acute coronary syndrome (ACS) and have an increased LDL-cholesterol (≥70 mg/dL) despite being treated with a statin drug,

Detailed Description
-----------------
The purpose of this study is to study the effectiveness of implementation of a systematic LDL-C management pathway including treatment with inclisiran in participants who have experienced a recent acute coronary syndrome (ACS) and have an increased LDL-cholesterol (≥70 mg/dL) despite being treated with a statin drug,

Official Title
-----------------
A Randomized, Controlled, Multicenter, Open-label Trial Comparing a Hospital Post-discharge Care Pathway Involving Aggressive LDL-C Management That Includes Inclisiran With Usual Care Versus Usual Care Alone in Patients With a Recent Acute Coronary Syndrome(VICTORION-INCEPTION)

Conditions
-----------------
Acute Coronary Syndrome

Intervention / Treatment
-----------------
* Drug: Inclisiran


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recent Acute Coronary Syndrome (in-patient/out-patient) within 5 weeks of screening Serum LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL Fasting triglycerides <4.52 mmol/L (<400 mg/dL) at screening Calculated glomerular filtration rate >20 mL/min by estimated glomerular filtration rate (eGFR) Participants are required to be discharged on statin therapy, or have documented statin intolerance, as determined by the investigator, following hospitalization for an ACS. Statin intolerant patients are eligible if they had intolerable side effects on at least 2 different statins, including one at the lowest standard dose Exclusion Criteria: New York Heart Association (NYHA) class IIIb or IV heart failure or last known left ventricular ejection fraction <25%. Significant cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation at the time of screening. Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years. Treatment with other investigational products or devices within 30 days or five half˗lives of the screening visit, whichever is longer. Planned use of other investigational products or devices during the course of the study. Treatment with monoclonal antibodies directed towards PCSK9 within 90 days of screening. Recurrent ACS event within 2 weeks prior to randomization. Coronary angiography and revascularization procedure (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) surgery) performed within 2 weeks prior to the randomization visit or planned after randomization.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inclisiran with Usual Care<br>Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran) | Drug: Inclisiran<br>* Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran)<br>* Other names: KJX839;|
| No Intervention: Usual Care<br>Usual Care Alone | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) | Inclisiran compared to usual care in reducing LDL-C [percent change] at Day 330 (Year 1) | Baseline and Day 330 | 
| Percentage (%) achieving change in low-density lipoprotein cholesterol (LDL-C) to <70 mg/dl | Inclisiran compared to usual care in achieving LDL-C reduction <70 mg/dl [percent achieved] at Day 330 (Year 1) | Baseline and Day 330 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) | Inclisiran compared to usual care in reducing LDL-C [absolute change] at Day 330 (Year 1) | Baseline to Day 330 | 
| Average percent change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit | Inclisiran compared to usual care on average percent change from baseline in LDL-C levels after Day 90 and up to Day 330 | Baseline, after Day 90 up to Day 330 | 
| Average absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit | Inclisiran compared to usual care on average absolute change from baseline in LDL-C levels after Day 90 and up to Day 330 | Baseline, after Day 90 up to Day 330 | 
| Achieving ≥ 50% reduction from baseline in low-density lipoprotein cholesterol (LDL-C) (yes, no) | Inclisiran compared to usual care on achieving ≥ 50% reduction from baseline in LDL-C after Day 90 and up to Day 330 | Baseline, after Day 90 up to Day 330 | 
| Percentage of participants achieving low-density lipoprotein cholesterol (LDL-C) targets (LDL-C < 100 mg/dL among the subset of participants with LDL-C ≥ 100 mg/dL at baseline, and LDL-C < 55 mg/dL) | Inclisiran compared to usual care on achieving LDL-C < 100 mg/dL (subset of LDL-C ≥ 100 mg/dL at baseline) and LDL-C <55 mg/dl after Day 90 and up to Day 330 | Baseline, after Day 90 up to Day 330 | 
| Percent change in apolipoprotein B, very low density lipoprotein, high density lipoprotein cholesterol, lipoprotein (a), non-high density lipoprotein cholesterol, and total cholesterol | Inclisiran compared to placebo in reducing Apo B, very low density lipoprotein (VLDL), high density lipoprotein cholesterol (HDL-C), lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol over time | Baseline and Day 330 | 
| Absolute change in apolipoprotein B, very low density lipoprotein, high density lipoprotein cholesterol, lipoprotein (a), non-high density lipoprotein cholesterol, and total cholesterol | Inclisiran compared to placebo in reducing Apo B, very low density lipoprotein (VLDL), high density lipoprotein cholesterol (HDL-C), lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol over time | Baseline and Day 330 | 
| Measurement of the intensity of lipid lowering therapy (dose decrease, increase or no change) | Inclisiran compared to usual care on intensity of lipid lowering therapy over time | Baseline and Day 330 | 
| Percentage of participants discontinuing statin therapy (i.e., no statin use ≥ 30 days before the end-of-study visit) | Inclisiran compared to usual care on discontinuation of statin therapy from baseline to Day 330 | Baseline and Day 330 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hyperlipidemia, Atherosclerotic Cardiovascular Disease, Hypercholesterolemia, Lipid lowering therapies