Clinical trial NCT05974345: In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atherosclerotic Cardiovascular Disease
Keywords: Atherosclerotic cardiovascular disease
Hypercholesterolemia
Dyslipidemia
High cholesterol
Hyperlipidemia
Inclisiran
siRNA
KJX839
Myocardial infarction
Ischemic stroke
Peripheral arterial disease
In silico model
In silico simulation
PCSK9 inhibitors
Arteriosclerosis
Atherosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-08-03
Enrollment: 204691
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Virtual Patient with ASCVD (previous MI, previous ischemic stroke, previous peripheral arterial disease) and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe.

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: 5 years of follow-up
measure: Time to the first occurrence between trial start and end of follow-up of CV death
timeFrame: 5 years of follow-up
Secondary outcomes:
measure: Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)
timeFrame: 5 years of follow-up
measure: Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal)
timeFrame: 5 years of follow-up
measure: Time to the first occurrence between trial start and end of follow-up of Major Adverse Limb events (MALE)
timeFrame: 5 years of follow-up
measure: Change in LDL-C from baseline to specified time points
timeFrame: baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary.
measure: Time adjusted percentage change in LDL-C
timeFrame: From baseline between Day 90 and the end of follow-up period (up to 5 years)
Other outcomes:
Locations:
city: Rueil-Malmaison
country: France
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: