Inclisiran for Cardiovascular Disease

(V-INCLUSION Trial)

Recruiting at 37 trial locations

Overseen By Michael Shapiro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must be taking: Statins

Must not be taking: PCSK9 antibodies, Inclisiran

Disqualifiers: Pregnancy, Heart failure, Arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 450

1440 Participants Needed

Trial Summary

What is the purpose of this trial?

VictORION-INCLUSION (V-INCLUSION) seeks to evaluate the effectiveness of inclisiran as an innovative therapy with the potential to help bridge care gaps in historically understudied and undertreated populations by leveraging electronic health records (EHR) in multiple US Healthcare Systems (HCS) to systematically identify those at high risk for and already diagnosed with ASCVD for more expeditious achievement of LDL-C targets.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on statin therapy or have documented statin intolerance to participate.

How is the drug Inclisiran unique for treating cardiovascular disease?

Inclisiran is unique because it works by targeting a specific protein involved in cholesterol production, which helps lower LDL cholesterol levels. It is administered as an injection only twice a year, making it more convenient compared to other treatments that require more frequent dosing. ^{1 2 3 4 5}

Research Team

Neha Pagidipati, MD

Principal Investigator

Duke Clinical Research Institute

Eligibility Criteria

The VictORION-INCLUSION trial is for adults over 18 with cardiovascular disease or at high risk, as noted in their health records. Participants must have LDL cholesterol above certain levels despite being on statins or having a documented intolerance to them. The study focuses on including underrepresented groups such as women, ethnic minorities, and rural residents.

Inclusion Criteria

I meet all the required conditions for the study.

I am 18 years old or older.

I am willing and able to follow the study's procedures after giving informed consent.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Randomized, controlled, multicenter, open-label trial comparing inclisiran and usual care versus usual care alone

52 weeks

Visits at Day 90, Day 270, and Day 360

Treatment Part 2

Single arm trial with usual care participants initiating inclisiran at Day 360, with additional doses on Day 450 and Day 630

36 weeks

Doses on Day 360, Day 450, and Day 630

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Inclisiran

Trial Overview This trial tests Inclisiran's ability to manage cholesterol in heart disease patients. It uses electronic health records from US Healthcare Systems to quickly identify and treat those at high risk or with diagnosed atherosclerotic cardiovascular disease (ASCVD) to lower LDL-C levels faster.

Participant Groups

Group I: Inclisiran Experimental Treatment 1 Intervention

Inclisiran + Usual Care

Group II: Usual Care Active Control 1 Intervention

Usual Care

Inclisiran is already approved in European Union, United States, China for the following indications:

Approved in European Union as Leqvio for:

• Primary hypercholesterolemia (heterozygous familial and non-familial)
• Mixed dyslipidemia

Approved in United States as Leqvio for:

• Heterozygous familial hypercholesterolemia (HeFH)
• Clinical atherosclerotic cardiovascular disease (ASCVD)
• Primary hypercholesterolemia

Approved in China as Leqvio for:

• Primary hypercholesterolemia (heterozygous familial and non-familial)
• Mixed dyslipidemia

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Tranilast is being tested in a large multicenter study involving 11,500 patients to see if it can effectively reduce the risk of restenosis after coronary revascularization procedures, with a focus on its mechanisms that inhibit smooth muscle cell proliferation and collagen synthesis.

This study is significant as it aims to confirm previous positive results seen in Japanese populations and assess whether tranilast can also lower clinical events like death and myocardial infarction in a Western population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial. Holmes, D., Fitzgerald, P., Goldberg, S., et al.[2019]

The XLIMUS sirolimus-eluting stent demonstrated a high delivery success rate of 98% in a study involving 200 patients with complex coronary artery lesions, indicating its effectiveness in challenging cases.

The 1-year rate of major adverse cardiac events (MACE) was 9%, suggesting that the XLIMUS SES is not only deliverable but also safe for patients undergoing percutaneous coronary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of the XLIMUS Sirolimus-Eluting Coronary Stent in Very Complex Lesions. Briguori, C., Visconti, G., Donahue, M., et al.[2022]

In a study of 84 patients with 89 coronary lesions, pemirolast significantly reduced the rate of restenosis after stent placement, with rates of 15.0% in the pemirolast group compared to 34.1% in the control group.

Pemirolast treatment resulted in a larger lumen cross-sectional area and smaller neointima area, suggesting it may prevent restenosis by inhibiting neointimal hyperplasia, which is the growth of tissue that can block the artery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies. Ohsawa, H., Noike, H., Kanai, M., et al.[2016]

The NEVO sirolimus-eluting stent (SES) demonstrated significantly less neointimal proliferation compared to the TAXUS Liberté paclitaxel-eluting stent (PES), resulting in better arterial response and less late lumen area loss after 6 months in a study of 100 patients.

The NEVO SES showed a more uniform distribution of neointimal thickness, indicating a more consistent performance, while the TAXUS PES exhibited greater positive vessel remodeling, suggesting different mechanisms of action between the two stent types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravascular ultrasound results from the NEVO ResElution-I trial: a randomized, blinded comparison of sirolimus-eluting NEVO stents with paclitaxel-eluting TAXUS Liberté stents in de novo native coronary artery lesions. Otake, H., Honda, Y., Courtney, BK., et al.[2016]

The Inspiron™ sirolimus-eluting stent (SES) demonstrated a significant reduction in the need for repeat revascularization procedures (0.0% vs. 23.5%) compared to the bare metal stent after 4 years, indicating its efficacy in long-term cardiac outcomes.

There were no occurrences of stent thrombosis in the study population, highlighting the safety of the Inspiron™ SES over the 4-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-year clinical follow-up of the first-in-man randomized comparison of a novel sirolimus eluting stent with abluminal biodegradable polymer and ultra-thin strut cobalt-chromium alloy: the INSPIRON-I trial. Oliveira, MD., Ribeiro, EE., Campos, CM., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Performance of the XLIMUS Sirolimus-Eluting Coronary Stent in Very Complex Lesions. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Intravascular ultrasound results from the NEVO ResElution-I trial: a randomized, blinded comparison of sirolimus-eluting NEVO stents with paclitaxel-eluting TAXUS Liberté stents in de novo native coronary artery lesions. [2016]

5. China pubmed.ncbi.nlm.nih.gov

Four-year clinical follow-up of the first-in-man randomized comparison of a novel sirolimus eluting stent with abluminal biodegradable polymer and ultra-thin strut cobalt-chromium alloy: the INSPIRON-I trial. [2020]