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

Atherosclerotic Cardiovascular Disease Clinical Trial

— SIRIUS  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05974345
• Other study ID #: CKJX839B1FR01
• Status: Active, not recruiting
• Start date: November 3, 2023
• Est. completion date: March 31, 2024

Study information

• Verified date: December 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 204691
• Est. completion date: March 31, 2024
• Est. primary completion date: November 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Inclisiran sodium
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: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.
• Ezetimibe
Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation.
• Evolocumab
Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Rueil-Malmaison

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	5 years of follow-up
Primary	Time to the first occurrence between trial start and end of follow-up of CV death	CV death is defined as death due to cardiovascular events	5 years of follow-up
Secondary	Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)	Myocardial infarction (MI)	5 years of follow-up
Secondary	Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal)		5 years of follow-up
Secondary	Time to the first occurrence between trial start and end of follow-up of Major Adverse Limb events (MALE)	MALE include acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia	5 years of follow-up
Secondary	Change in LDL-C from baseline to specified time points	Low density lipoprotein cholesterol (LDL-C)	baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary.
Secondary	Time adjusted percentage change in LDL-C	This is the average percentage change in LDL-C from baseline over period from Day 90 and the end of follow-up period.	From baseline between Day 90 and the end of follow-up period (up to 5 years)