A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease (ORION-4)
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|ClinicalTrials.gov Identifier: NCT03705234|
Recruitment Status : Recruiting
First Posted : October 15, 2018
Last Update Posted : September 16, 2022
|Condition or disease||Intervention/treatment||Phase|
|Atherosclerotic Cardiovascular Disease||Drug: Inclisiran Drug: Placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15000 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||HPS-4/TIMI 65/ORION-4: A Double-blind Randomized Placebo-controlled Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Atherosclerotic Cardiovascular Disease|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||July 2026|
|Estimated Study Completion Date :||December 2049|
Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Placebo Comparator: Placebo
Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Other Name: Saline solution
- Number of participants with a major adverse cardiovascular event (MACE) [ Time Frame: 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.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03705234
|Contact: Louise Bowman||+44 (0)1865 firstname.lastname@example.org|
|Contact: Marion Mafham||+44 (0)1865 email@example.com|
|United States, Massachusetts|
|TIMI Study Group||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: David Morrow, MD, MPH 617-278-0145 TIMI@partners.org|
|Contact: Michelle O'Donoghue, MD, MPH 617-278-0145 TIMI@partners.org|
|CTSU, University of Oxford||Recruiting|
|Oxford, Oxfordshire, United Kingdom, OX3 7LF|
|Contact: Louise Bowman|
|Principal Investigator:||Louise Bowman||University of Oxford|
|Principal Investigator:||Marion Mafham||University of Oxford|
|Principal Investigator:||David Preiss||University of Oxford|
|Principal Investigator:||Martin Landray||University of Oxford|