16124 Participants Needed

Inclisiran for Cardiovascular Disease

(ORION-4 Trial)

Recruiting at 2 trial locations
LB
MM
Overseen ByMarion Mafham
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are currently or have recently been treated with a monoclonal antibody targeting PCSK9, you may not be eligible to participate.

What makes the drug Inclisiran unique for treating cardiovascular disease?

Inclisiran is unique because it works by targeting and reducing the production of a specific protein involved in cholesterol regulation, which is different from other treatments that typically focus on blocking cholesterol absorption or production directly. It is administered as an injection every six months, offering a convenient dosing schedule compared to daily medications.12345

What is the purpose of this trial?

This trial tests inclisiran, a new injection to lower cholesterol, in people who have had heart attacks, strokes, or surgeries for blocked arteries. It works by blocking a protein that produces bad cholesterol.

Research Team

MM

Marion Mafham

Principal Investigator

University of Oxford

DP

David Preiss

Principal Investigator

University of Oxford

LB

Louise Bowman

Principal Investigator

University of Oxford

ML

Martin Landray

Principal Investigator

University of Oxford

Eligibility Criteria

This trial is for men over 40 and women over 55 with a history of heart attack, stroke, or procedures for blocked arteries. It's not open to those planning heart surgery soon, with chronic liver disease, on dialysis/transplantation, pregnant/breastfeeding women, or anyone with severe illnesses that could interfere with the study.

Inclusion Criteria

You have been diagnosed with Hypercholesterolemia
Have you at least 4 weeks of been taking statins

Exclusion Criteria

You have been diagnosed with Stroke
I have previously used inclisiran or been in a study for it.
I am scheduled for a heart artery procedure in the next 6 months.
See 4 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inclisiran or placebo via subcutaneous injection at randomization, 3 months, and then every 6 months

5 years
Injections at randomization, 3 months, and every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

  • Inclisiran
  • Placebo
Trial Overview ORION-4 is testing whether inclisiran injections can reduce the risk of heart attacks and strokes in people who've already had cardiovascular events. Participants will be randomly assigned to receive either inclisiran or a placebo.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: InclisiranExperimental Treatment1 Intervention
Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.
Group II: PlaceboPlacebo Group1 Intervention
Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Oxford

Lead Sponsor

Trials
1,113
Recruited
21,220,000+

The TIMI Study Group

Collaborator

Trials
22
Recruited
129,000+

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 profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

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

Performance of the XLIMUS Sirolimus-Eluting Coronary Stent in Very Complex Lesions. [2022]
The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial. [2019]
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]
Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies. [2016]
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]
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