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

Novartis

Status: Completed

Conditions: Atherosclerotic Cardiovascular Disease

Treatments: Drug: Evolocumab; Drug: Inclisiran sodium; Drug: Ezetimibe; Drug: Placebo

Study type: Observational

Funder types: Industry

Identifiers

NCT05974345

CKJX839B1FR01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 204,691 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

204,691 participants in 1 patient group

Virtual Patient with ASCVD

Description:

Virtual Patient with ASCVD and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe. Each virtual patient is his own control.

Treatment:

Drug: Inclisiran sodium

Drug: Placebo

Drug: Ezetimibe

Drug: Evolocumab