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NCT Number: NCT05974345

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

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.

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Key information

Conditions

Atherosclerotic Cardiovascular Disease Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Dyslipidemias Heart Diseases Hypercholesterolemia Hyperlipidemias Infarction Ischemia Ischemic Stroke Lipid Metabolism Disorders Metabolic Diseases Myocardial Infarction Myocardial Ischemia Necrosis Nervous System Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral Arterial Disease Peripheral Vascular Diseases Stroke Vascular Diseases

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Novartis Investigative Site

Rueil-Malmaison, 92563, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

  • Fasting LDL-C ≥ 70 mg/dL
  • 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

Treatment and study plan

Inclisiran Sodium

Drug

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

Placebo

Drug

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

ezetimibe

Drug

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

Evolocumab

Drug

Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.

Primary outcomes

  1. 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)

    Time frame: 5 years of follow-up

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

  2. Time to the first occurrence between trial start and end of follow-up of CV death

    Time frame: 5 years of follow-up

    CV death is defined as death due to cardiovascular events

Secondary outcomes

  1. Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)

    Time frame: 5 years of follow-up

    Myocardial infarction (MI)

  2. Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal)

    Time frame: 5 years of follow-up

  3. Time to the first occurrence between trial start and end of follow-up of Major Adverse Limb events (MALE)

    Time frame: 5 years of follow-up

    MALE include acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia

  4. Change in LDL-C from baseline to specified time points

    Time frame: baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary.

    Low density lipoprotein cholesterol (LDL-C)

  5. Time adjusted percentage change in LDL-C

    Time frame: From baseline between Day 90 and the end of follow-up period (up to 5 years)

    This is the average percentage change in LDL-C from baseline over period from Day 90 and the end of follow-up period.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

In Silico Non Interventional Secondary Use of Data Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease

Acronym: SIRIUS

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Aug 3, 2023
Registry last updated
May 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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