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Dual PCSK9 Inhibition With Inclisiran and Alirocumab in Secondary Prevention (PCSK9-DUO)

2026年5月28日 更新者：University Medical Centre Ljubljana

PCSK9-DUO Trial: Dual PCSK9 Inhibition With Inclisiran and Alirocumab in Patients With High Cardiovascular Risk in Secondary Prevention

This study will evaluate the effectiveness and safety of combining two different types of PCSK9 inhibitors, inclisiran and alirocumab, in patients with high cardiovascular risk who are unable to tolerate statins.

Lowering low-density lipoprotein cholesterol (LDL-C) is essential to reduce the risk of cardiovascular events. While PCSK9 inhibitors are effective, many patients treated with a single agent do not reach recommended LDL-C targets, especially those who cannot take statins.

Inclisiran and alirocumab reduce LDL-C through different mechanisms. Inclisiran decreases the production of PCSK9 in the liver, while alirocumab binds circulating PCSK9 in the blood. Combining these therapies may lead to a greater reduction in LDL-C levels.

In this randomized, open-label clinical trial, approximately 60 patients in secondary prevention will be assigned to one of three groups: inclisiran alone, alirocumab alone, or a combination of both treatments. Patients will be followed for 9 months with regular clinical and laboratory assessments.

The main goal of the study is to determine whether combination therapy leads to greater LDL-C reduction compared to each treatment alone. Secondary objectives include assessing the proportion of patients achieving target LDL-C levels and evaluating treatment safety and tolerability.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality, with elevated low-density lipoprotein cholesterol (LDL-C) being a major modifiable risk factor. Despite the availability of effective lipid-lowering therapies, a substantial proportion of high-risk patients fail to achieve recommended LDL-C targets, particularly those with statin intolerance.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating LDL receptor degradation and plasma LDL-C levels. Pharmacological inhibition of PCSK9 has emerged as an effective strategy to reduce LDL-C. Two distinct therapeutic approaches are currently available: monoclonal antibodies (such as alirocumab), which neutralize circulating PCSK9, and small interfering RNA therapies (such as inclisiran), which reduce hepatic production of PCSK9.

Although both approaches have demonstrated efficacy, real-world data suggest that monotherapy may not be sufficient for many high-risk patients. The combination of these two mechanisms may provide additive or synergistic effects, leading to more profound LDL-C reduction.

This study is designed as a prospective, randomized, open-label, monocentric clinical trial. Approximately 60 adult patients in secondary prevention with statin intolerance and elevated LDL-C (2.5-5.0 mmol/L) will be enrolled. Participants will be randomized in a 1:1:1 ratio to receive inclisiran, alirocumab, or a combination of both therapies.

Inclisiran will be administered subcutaneously at baseline and at 3 months. Alirocumab will be administered subcutaneously at a dose of 300 mg every 4 weeks in a supervised clinical setting. Patients will be followed for 9 months, with study visits at baseline, 1 month, 3 months, 6 months, and 9 months.

The primary endpoint is the percentage change in LDL-C from baseline at 3 and 9 months. Secondary endpoints include the proportion of patients achieving guideline-recommended LDL-C targets, changes in other lipid parameters, and safety outcomes including adverse events and treatment tolerability.

This study aims to provide proof-of-concept evidence on the effectiveness and safety of dual PCSK9 inhibition using complementary mechanisms, with potential implications for improving lipid management in high-risk, statin-intolerant patients.

研究类型

介入性

注册 (估计的)

60

阶段

  • 第四阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 斯洛文尼亚
      • Ljubljana、斯洛文尼亚、1000
        • 招聘中
        • University Medical Centre Ljubljana
        • 接触：
        • 接触：
        • 首席研究员：
          • Jan Kafol, MD
        • 副研究员：
          • Zlatko Fras, MD, PhD
        • 副研究员：
          • Borut Jug, MD, PhD
        • 副研究员：
          • Marko Novakovic, MD, PhD

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  • Adults aged ≥18 years
  • Established atherosclerotic cardiovascular disease (secondary prevention), defined as prior cardiovascular events or imaging-confirmed atherosclerosis (e.g., coronary artery disease on angiography or CT, carotid plaque on ultrasound, or peripheral arterial disease).
  • Eligible for PCSK9 inhibitor therapy according to national clinical criteria
  • Fasting LDL cholesterol ≥2.5 mmol/L and ≤5.0 mmol/L at screening
  • Documented statin intolerance or contraindication to statin therapy
  • On stable background lipid-lowering therapy (including ezetimibe if applicable) for at least 4 weeks prior to enrollment
  • Able and willing to provide written informed consent

Exclusion Criteria:

  • Eligibility for PCSK9 inhibitor therapy solely based on elevated lipoprotein(a) >1000 mg/L with LDL-C below inclusion threshold
  • Prior use of any PCSK9 inhibitor (alirocumab, evolocumab or inclisiran) before enrollment
  • Planned initiation or modification of lipid-lowering therapy during the study period
  • Known homozygous familial hypercholesterolemia
  • Active liver disease or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper limit of normal
  • Severe renal impairment (eGFR <30 mL/min/1.73 m²)
  • Active malignancy or life expectancy <1 year
  • Pregnancy, breastfeeding, or women of childbearing potential not using effective contraception
  • Known hypersensitivity to inclisiran, alirocumab, or any of their excipients
  • Participation in another interventional clinical trial within 30 days prior to enrollment
  • Any condition that, in the opinion of the investigator, would interfere with study participation or interpretation of results

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Inclisiran
Participants receive inclisiran 284 mg administered subcutaneously at baseline and at 3 months. Patients will be followed for 9 months with scheduled clinical and laboratory assessments.
药品：Inclisiran
Participants receive inclisiran 284 mg administered subcutaneously at baseline (Day 0) and at Month 3.
实验性的：Alirocumab
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months. Patients will be followed with regular clinical and laboratory assessments.
药品：Alirocumab
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months.
实验性的：Inclisiran Plus Alirocumab
Participants receive inclisiran 284 mg administered subcutaneously at baseline and at 3 months, in combination with alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months. Patients will be followed with scheduled clinical and laboratory assessments.
药品：Inclisiran
Participants receive inclisiran 284 mg administered subcutaneously at baseline (Day 0) and at Month 3.
药品：Alirocumab
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Percent Change in LDL-C From Baseline
大体时间：3 months and 9 months
Percent change in low-density lipoprotein cholesterol (LDL-C) from baseline at 3 months and 9 months, comparing inclisiran, alirocumab, and combination therapy.
3 months and 9 months

次要结果测量

结果测量
措施说明
大体时间
Trajectory of Percent Change in LDL-C From Baseline
大体时间：1, 3, 6, and 9 months
Percent change in LDL-C from baseline at each scheduled follow-up visit to assess early response and durability of treatment effect.
1, 3, 6, and 9 months
Proportion of Participants Achieving LDL-C <1.4 mmol/L
大体时间：1, 3, 6, and 9 months
Proportion of participants achieving LDL-C below 1.4 mmol/L at each scheduled follow-up visit.
1, 3, 6, and 9 months
Change in Apolipoprotein B From Baseline
大体时间：1, 3, 6, and 9 months
Absolute and percent change in apolipoprotein B from baseline.
1, 3, 6, and 9 months
Change in Non-HDL Cholesterol From Baseline
大体时间：1, 3, 6, and 9 months
Absolute and percent change in non-HDL cholesterol from baseline.
1, 3, 6, and 9 months
Change in Lipoprotein(a) From Baseline
大体时间：1, 3, 6, and 9 months
Absolute and percent change in lipoprotein(a) from baseline.
1, 3, 6, and 9 months
Incidence of Adverse Events
大体时间：Up to 9 months
Number and proportion of participants experiencing any adverse event during the study.
Up to 9 months
Treatment Discontinuation Due to Adverse Events
大体时间：Up to 9 months
Proportion of participants who discontinue assigned study treatment because of adverse events.
Up to 9 months
Change in Circulating PCSK9 Concentration From Baseline
大体时间：1, 3, 6, and 9 months
Absolute and percent change in circulating PCSK9 concentration to assess pharmacodynamic effects of treatment.
1, 3, 6, and 9 months
Change From Baseline in LDL-C Concentration
大体时间：1, 3, 6, and 9 months
Absolute change in LDL-C concentration compared with baseline at each scheduled follow-up visit.
1, 3, 6, and 9 months
Change From Baseline in Total Cholesterol, HDL Cholesterol, and Triglyceride Concentrations
大体时间：1, 3, 6, and 9 months
Change in serum total cholesterol, HDL cholesterol, and triglyceride concentrations compared with baseline values.
1, 3, 6, and 9 months

其他结果措施

结果测量
措施说明
大体时间
Incidence of Injection-Site Reactions
大体时间：Up to 9 months
Number and proportion of participants experiencing injection-site reactions.
Up to 9 months
Treatment Adherence
大体时间：Up to 9 months
Adherence to assigned therapy assessed by documented administration of inclisiran and alirocumab.
Up to 9 months
Major Adverse Cardiovascular Events
大体时间：Up to 9 months
Exploratory assessment of cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization, or hospitalization for unstable angina.
Up to 9 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University Medical Centre Ljubljana

调查人员

  • 学习椅：Zlatko Fras, MD, PhD、University Medical Centre Ljubljana
  • 首席研究员：Jan Kafol, MD、University Medical Centre Ljubljana

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年5月18日

初级完成 (估计的)

2027年5月1日

研究完成 (估计的)

2027年6月1日

研究注册日期

首次提交

2026年5月5日

首先提交符合 QC 标准的

2026年5月5日

首次发布 (实际的)

2026年5月12日

研究记录更新

最后更新发布 (实际的)

2026年6月2日

上次提交的符合 QC 标准的更新

2026年5月28日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • UKC-PCSK9-DUO

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

De-identified individual participant data (IPD) underlying the results reported in this study will be made available upon reasonable request to qualified researchers. Data sharing will be subject to approval by the study investigators and institutional policies, and will require a data use agreement to ensure appropriate use and protection of participant confidentiality.

IPD 共享时间框架

Individual participant data and supporting documents will be available beginning 6 months following publication of the primary results and ending 5 years after publication.

IPD 共享访问标准

De-identified individual participant data, study protocol, statistical analysis plan, and informed consent form will be made available to qualified researchers who provide a methodologically sound research proposal. Data access will be subject to approval by the study investigators and the sponsoring institution. A data use agreement will be required to ensure appropriate use of the data and protection of participant confidentiality. Requests for access should be directed to the principal investigator.

IPD 共享支持信息类型

  • 研究方案
  • 树液
  • 国际碳纤维联合会

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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