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A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease

Phase 3
Active, not recruiting
Conditions
Atherosclerotic Cardiovascular Disease
Interventions
Drug: Placebo
Registration Number
NCT03705234
Lead Sponsor
University of Oxford
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
16124
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.
InclisiranInclisiranInclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.
Primary Outcome Measures
NameTimeMethod
Number of participants with a major adverse cardiovascular event (MACE)Median follow-up of 5-years

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.

Secondary Outcome Measures
NameTimeMethod
Number of participants with MACE among those recorded to be taking high-intensity statin at baselineMedian follow-up of 5-years
Number of participants with a composite of CHD death or myocardial infarctionMedian follow-up of 5-years
Number of participants with cardiovascular deathMedian follow-up of 5-years

Trial Locations

Locations (2)

CTSU, University of Oxford

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Oxford, Oxfordshire, United Kingdom

TIMI Study Group

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Boston, Massachusetts, United States

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