Atherosclerotic Cardiovascular DiseaseSIRIUSNCT05974345
In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease
An observational study of Atherosclerotic Cardiovascular Disease, run by Novartis Pharmaceuticals at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Atherosclerotic Cardiovascular Disease
- What is being tested?
- Inclisiran sodium, Ezetimibe and Evolocumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 204,691 participants
- Where
- 1 siteFrance
- Study dates
- 3 Nov 2023to 15 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Patients with atherosclerotic CV disease, defined as any of the following
- Previous MI
- Previous ischemic stroke
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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 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.
Read the 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.
- Conditions
- Atherosclerotic Cardiovascular Disease
- Being tested
- Inclisiran sodium, Placebo, Ezetimibe, Evolocumab
- 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
- Medical subject headings
- Atherosclerosis, Hypercholesterolemia, Dyslipidemias, Hyperlipidemias, Myocardial Infarction, Ischemic Stroke, Peripheral Arterial Disease, Arteriosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
EvolocumabDrug
Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.
| Study group | Role | What they receive |
|---|---|---|
| Virtual Patient with ASCVD | 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. Receives: Drug: Inclisiran sodium; Drug: Placebo; Drug: Ezetimibe; Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years of follow-up
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
Measured: 5 years of follow-up
Secondary outcomes (5)
Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)
Myocardial infarction (MI)
Measured: 5 years of follow-up
Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal)
Measured: 5 years of follow-up
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
Measured: 5 years of follow-up
Change in LDL-C from baseline to specified time points
Low density lipoprotein cholesterol (LDL-C)
Measured: baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary.
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.
Measured: From baseline between Day 90 and the end of follow-up period (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2023
- Study start3 Nov 2023
- Primary completion15 Dec 2023
- Study completion15 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atherosclerotic Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 204,691 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05974345
- Sponsor's protocol ID
- CKJX839B1FR01
- Acronym
- SIRIUS
- Status last verified
- May 2024
- First submitted
- 26 Jul 2023
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Angoulvant D, Granjeon-Noriot S, Amarenco P, Bastien A, Bechet E, Boccara F, Boissel JP, Cariou B, Courcelles E, Diatchenko A, Filipovics A, Kahoul R, Mahe G, Peyronnet E, Portal L, Porte S, Wang Y, Steg PG. In-silico trial emulation to predict the cardiovascular protection of new lipid-lowering drugs: an illustration through the design of the SIRIUS programme. Eur J Prev Cardiol. 2024 Nov 11;31(15):1820-1830. doi: 10.1093/eurjpc/zwae254.
PubMed 39101472
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05974345
- Acronym / sponsor ID
- SIRIUS / CKJX839B1FR01
- Conditions
- Atherosclerotic Cardiovascular Disease
- Keywords
- Atherosclerotic cardiovascular disease, Hypercholesterolemia, Dyslipidemia, High cholesterol, Hyperlipidemia, Inclisiran, siRNA, KJX839
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 204,691 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 3 Nov 2023 (actual)
- Primary completion
- 15 Dec 2023 (actual)
- Study completion
- 15 Dec 2023 (actual)
- First posted
- 3 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Virtual Patient with ASCVD | – | Drug: Inclisiran sodium, Drug: Placebo, Drug: Ezetimibe, Drug: EvolocumabVirtual 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- Patients with atherosclerotic CV disease, defined as any of the following
- Fasting LDL-C ≥ 70 mg/dL
- Under stable (≥ 4 weeks) well-tolerated high-intensity statin with or without ezetimibe.
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inclisiran sodiumDrug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation. | Drug | Virtual Patient with ASCVD |
| PlaceboDrug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation. | Drug | Virtual Patient with ASCVD |
| EzetimibeDrug: Ezetimibe 10 mg virtually orally once a day until end of simulation. | Drug | Virtual Patient with ASCVD |
| EvolocumabDrug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation. | Drug | Virtual Patient with ASCVD |
Primary outcome
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.
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
5 secondary outcomes
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
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
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
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.
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Derived from this study: PubMed 39101472Angoulvant D, Granjeon-Noriot S, Amarenco P, Bastien A, Bechet E, Boccara F, Boissel JP, Cariou B, Courcelles E, Diatchenko A, Filipovics A, Kahoul R, Mahe G, Peyronnet E, Portal L, Porte S, Wang Y, Steg PG. In-silico trial emulation to predict the cardiovascular protection of new lipid-lowering drugs: an illustration through the design of the SIRIUS programme. Eur J Prev Cardiol. 2024 Nov 11;31(15):1820-1830. doi: 10.1093/eurjpc/zwae254.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerotic Cardiovascular Disease, run by Novartis Pharmaceuticals at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 5 years of follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05974345, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.