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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 16,124
- 试验地点
- 4
- 主要终点
- Number of participants with a major adverse cardiovascular event (MACE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History or evidence of at least one of the following:
- •Prior MI; or
- •Prior ischemic stroke; or
- •Peripheral artery disease as evident by prior lower extremity artery revascularization or aortic aneurysm repair.
- •Minimum age is 40 years for men and 55 years for women
排除标准
- •None of the following must be satisfied (based on self-reported medical history):
- •Acute coronary syndrome or stroke less than 4 weeks before the Screening visit or during the Run-in period;
- •Coronary revascularization procedure planned within the next 6 months;
- •Known chronic liver disease;
- •Current or planned renal dialysis or transplantation;
- •Previous exposure to inclisiran or participation in a randomized trial of inclisiran;
- •Previous (within about 3 months), current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran (none currently known);
- •Known to be poorly compliant with clinic visits or prescribed medication;
- •Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease; cancer or evidence of spread within approximately the last 5 years, other than non-melanoma skin cancer; or history of alcohol or substance misuse) or may put the individual at significant risk in the opinion of the investigator (or their authorised deputy) if he/she were to participate in the trial;
- •Women of child-bearing potential, current pregnancy, or lactation;
- •Current participation in a clinical trial with an unlicensed drug or device; or
- •Staff personnel directly involved with the study and any family member of the investigational study staff.
研究组 & 干预措施
Placebo
Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.
干预措施: Placebo (Drug)
Inclisiran
Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.
干预措施: Inclisiran (Drug)
结局指标
主要结局
Number of participants with a major adverse cardiovascular event (MACE)
时间窗: 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.
次要结局
- Number of participants with MACE among those recorded to be taking high-intensity statin at baseline(Median follow-up of 5-years)
- Number of participants with a composite of CHD death or myocardial infarction(Median follow-up of 5-years)
- Number of participants with cardiovascular death(Median follow-up of 5-years)