In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease

Novartis Pharmaceuticals204,691 enrolled

Overview

Study CKJX839B1FR01 in an In silico trial to predict the efficacy of Inclisiran therapy on major adverse cardiovascular events (MACE) and cardiovascular (CV) death in virtual patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.

Purpose of this study is to predict the size of efficacy of inclisiran 300 mg s.c., administered on Day 1, Month 3 (Day 90), and every 6 months thereafter in addition to currently available lipid lowering therapies (LLTs) on a 3-Point-Major Adverse Cardiovascular Events (3P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI) or non-fatal ischemic stroke, and on CV death, in a secondary prevention cohort of ASCVD virtual patients with a LDL-C ≥ 70 mg/dL. This will be compared to 1) placebo in adjunct to high-intensity statin therapy with or without ezetimibe, 2) ezetimibe in adjunct to high-intensity statin therapy, 3) Evolocumab in adjunct to high-intensity statin therapy and ezetimibe.

Study Type

OBSERVATIONAL

Enrollment

204,691

Conditions

Atherosclerotic Cardiovascular Disease

Interventions

Inclisiran sodiumDRUG

Drug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.

PlaceboDRUG

Drug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.

EzetimibeDRUG

Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria : 1. Patients with atherosclerotic CV disease, defined as any of the following i. Previous MI ii. Previous ischemic stroke iii. Previous symptomatic peripheral arterial disease (PAD) as evidenced by either intermittent claudication with ABI \<0.85, prior peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease 2. Fasting LDL-C ≥ 70 mg/dL 3. Under stable (≥ 4 weeks) well-tolerated high-intensity statin with or without ezetimibe. Exclusion Criteria : Patients with acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \<4 weeks prior to the first study visit

Locations (1)

Novartis Investigative Site

Rueil-Malmaison, France

Outcomes

Primary Outcomes

Time to the first occurrence between trial start and end of follow-up of any component of 3P-MACE (composite of CV death, non-fatal MI or non-fatal ischemic stroke)

3P-MACE is a confirmed composite endpoint which includes cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke.