A Phase 3 interventional study of Inclisiran and Placebo in Atherosclerotic Cardiovascular Disease, sponsored by University of Oxford. Active, not recruiting at 2 sites in 2 countries. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2026-05-01.
Sponsored by University of Oxford · Phase 3, Interventional, and Prevention
ORION-4 is a research study coordinated by the University of Oxford and co-sponsored by The University of Oxford and Novartis (Protocol: CTSU_MDCO-PCS-17-01 (CKJX839B12301)). The study aims to find out if a new cholesterol-lowering injection (inclisiran) safely lowers the risk of heart attacks and strokes in people who have already had one of these conditions, or who have had an operation or procedure to treat blocked arteries.
The ORION-4 study aims to provide evidence about both the efficacy and safety of inclisiran. Inclisiran is a PCKS9 synthesis inhibitor which has been found to reduce LDL-cholesterol by about 50-60%. ORION-4 will investigate the effects of inclisiran on major adverse cardiovascular events.
The study is intended to be conducted at approximately 180 clinical sites in the UK and the USA. Approximately 15,000 participants aged 40 years or older for men, and 55 years or older for women, with pre-existing atherosclerotic cardiovascular disease will be randomized between inclisiran sodium 300 mg and matching placebo (given by subcutaneous injection on the day of randomization, at 3 months and then every 6-months) in a 1:1 ratio for a planned median duration of about 5 years.
1,567 studies on the registry are indexed under Atherosclerosis; 264 are open to participants now.
This study's enrollment of 16,124 is above the median of 106 across 882 interventional studies indexed under Atherosclerosis.
Browse Atherosclerosis studies →University of Oxford is the lead sponsor of 794 studies on the registry; 117 are open to participants now.
Counted across the registry records on this site, refreshed daily.
History or evidence of at least one of the following:
Minimum age is 40 years for men and 55 years for women
Exclusion Criteria
None of the following must be satisfied (based on self-reported medical history):
Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.
Drug: Inclisiran
Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.
Drug: Placebo
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Also known as: Saline solution
Number of participants with a major adverse cardiovascular event (MACE)
Defined as time to first occurrence - during the scheduled treatment period - of: * Coronary heart disease (CHD) death; * Myocardial infarction; * Fatal or non-fatal ischemic stroke; or * Urgent coronary revascularization procedure.
Time frame: Median follow-up of 5-years
Number of participants with MACE among those recorded to be taking high-intensity statin at baseline
Time frame: Median follow-up of 5-years
Number of participants with a composite of CHD death or myocardial infarction
Time frame: Median follow-up of 5-years
Number of participants with cardiovascular death
Time frame: Median follow-up of 5-years
Plan to share: Yes — Proposals for substudies must be approved by the Steering Committee. Procedure for accessing the data for this study are available on https://www.ndph.ox.ac.uk/data-access
Supporting information: Study protocol, Sap
This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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