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Reduced-Dose Thrombolysis in Intermediate-Risk Pulmonary Embolism With High-Risk Features (REDUCTION)

2026年11月2日 更新者：China National Center for Cardiovascular Diseases

Reduced-Dose Thrombolysis in Intermediate-High Risk Pulmonary Embolism, a Multicenter, Randomized Controlled Trial

Alteplase, a recombinant tissue plasminogen activator (rt-PA), is commonly used for thrombolytic treatment in patients with high-risk acute pulmonary thromboembolism (PTE), whereas the role of thrombolysis in intermediate-risk PTE remains controversial. This multicenter, randomized controlled trial will compare the efficacy and safety of reduced-dose alteplase (25 mg administered intravenously over 2 hours) plus standard anticoagulation with standard anticoagulation alone in patients with intermediate-risk PTE who have high-risk features.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

In patients with intermediate-risk pulmonary embolism (PE), full-dose systemic thrombolysis has been associated with a reduction in the risk of hemodynamic decompensation but an increased risk of major and intracranial bleeding. Previous studies suggest that reduced-dose thrombolysis may improve right ventricular (RV) function while potentially reducing bleeding complications. However, evidence regarding the efficacy and safety of reduced-dose systemic thrombolysis in patients with intermediate risk PE and additional high-risk clinical features remains limited. This study aims to evaluate the efficacy and safety of reduced-dose thrombolytic therapy in this patient population.

The REDUCTION study is a multicenter, randomized, open-label, controlled trial with blinded endpoint assessment and long-term follow-up.

Eligible patients will be randomly assigned in a 1:1 ratio to receive reduced-dose alteplase combined with standard anticoagulation or standard anticoagulation alone. Randomization will be centrally managed and stratified by participating center.

Patients will receive:

  • Reduced-dose alteplase group: Alteplase 25 mg administered by intravenous infusion over 2 hours, followed by standard anticoagulation with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) for at least 5 days.
  • Standard anticoagulation group: Standard anticoagulation with LMWH or UFH for at least 5 days without thrombolytic therapy.

The primary objective is to assess the efficacy of reduced-dose alteplase in improving RV function at 48 hours, as measured by the change in the ratio of right ventricular to left ventricular end-diastolic diameters (RVED/LVED) on echocardiography.

The secondary objectives are to evaluate early changes in right ventricular function, clinical deterioration, PE-related mortality, recurrent PE, and bleeding complications. Long-term assessments will evaluate persistent dyspnea, functional status, persistent right ventricular dysfunction, and the occurrence of chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH)

研究类型

介入性

注册 (估计的)

270

阶段

  • 第三阶段

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

  • 姓名：Changming Xiong, Prof.
  • 电话号码：(+86)010-88396798
  • 邮箱：xiongcmfw@163.com

学习地点

  • 中国
      • Beijing、中国、100037
        • Chinese Academy of Medical Sciences, Fuwai Hospital
        • 接触：
    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100029
        • China-Japan Friendship Hospital
        • 接触：
      • Beijing、Beijing Municipality、中国、100730
        • Peking Union Medical College Hospital
        • 接触：
          • Juhong Shi, Prof.
          • 电话号码：010-69156114
          • 邮箱：shijh@pumch.cn
      • Beijing、Beijing Municipality、中国、100029
        • Beijing Anzhen Hospital, Capital Medical University
        • 接触：
      • Beijing、Beijing Municipality、中国、100020
        • Beijing ChaoYang Hospital.Capital Medical University
        • 接触：
    • Guangdong
      • Guangzhou、Guangdong、中国、510120
        • Guangdong Provincial Hospital of Chinese Medicine
        • 接触：
      • Guangzhou、Guangdong、中国、510120
        • The First Affiliated Hospital of Guangzhou Medical University / Guangzhou Institute of Respiratory Health (National Clinical Research Center for Respiratory Disease)
        • 接触：
      • Shenzhen、Guangdong、中国、518116
        • Longgang Central Hospital of Shenzhen
        • 接触：
    • Hebei
      • Zhangjiakou、Hebei、中国、075000
        • The First Affiliated Hospital of Hebei North University
        • 接触：
    • Henan
      • Xinxiang、Henan、中国、453400
        • HeNan Honliv Hospital
        • 接触：
      • Zhengzhou、Henan、中国、450052
        • The First Affiliated Hospital of Zhengzhou University
        • 接触：
      • Zhengzhou、Henan、中国、450003
        • Henan Provincial People's Hospital
        • 接触：
    • Hubei
      • Wuhan、Hubei、中国、430015
        • Wuhan Sixth Hospital (Affiliated Hospital of Jianghan University)
        • 接触：
    • Inner Mongolia
      • Baotou、Inner Mongolia、中国、014010
        • Inner Mongolia Baogang Hospital
        • 接触：
      • Tongliao、Inner Mongolia、中国、028000
        • NMG Keerqin District Hosp.
        • 接触：
    • Jiangsu
      • Changzhou、Jiangsu、中国、213003
        • The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University
        • 接触：
      • Nanjing、Jiangsu、中国、210006
        • Nanjing First Hospital
        • 接触：
    • Liaoning
      • Shenyang、Liaoning、中国、110024
        • Central Hospital Affiliated to Shenyang Medical College
        • 接触：
          • Shuyue Xia, Prof.
          • 电话号码：024-85715200
          • 邮箱：syx262@126.com
      • Shenyang、Liaoning、中国、110003
        • General Hospital of Northern Theater Command
        • 接触：
    • Ningxia
      • Yinchuan、Ningxia、中国、750004
        • Ningxia Medical University General Hospital
        • 接触：
    • Shandong
      • Jinan、Shandong、中国、250021
        • Shandong Provincial Hospital
        • 接触：
      • Linyi、Shandong、中国、276000
        • Linyi People's Hospital
        • 接触：
    • Shanghai Municipality
      • Shanghai、Shanghai Municipality、中国、200120
        • Shanghai East Hospital, School of Medicine, Tongji University
        • 接触：
    • Sichuan
      • Chengdu、Sichuan、中国、610041
        • West China Hospital, Sichuan University
        • 接触：
    • Tianjin Municipality
      • Tianjin、Tianjin Municipality、中国、300052
        • Tianjin Medical University General Hospital
        • 接触：
      • Tianjin、Tianjin Municipality、中国、300222

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

18年 至 75年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Age 18 to 75 years

  • Objectively confirmed acute pulmonary thromboembolism (PTE) with symptom onset within 14 days, based on at least one of the following:

    1. Ventilation/perfusion lung scan showing at least one segmental or larger mismatched perfusion defect;
    2. Computed tomography pulmonary angiography (CTPA) or pulmonary angiography showing a filling defect or abrupt obstruction in a segmental or more proximal pulmonary artery.

  • Intermediate-high-risk PTE, with both of the following:

    1. Right ventricular dysfunction (RVD) on echocardiography or CTPA. Echocardiographic RVD is defined by at least one of the following:(1) right ventricular dilation with RV/LV end-diastolic diameter ratio >1.0; (2) reduced right ventricular free-wall motion; (3) increased tricuspid regurgitation velocity;(4) tricuspid annular plane systolic excursion <16 mm; (5) tricuspid annular systolic velocity (S') <9.5 cm/s. CTPA evidence of RVD is defined as right ventricular dilation with RV/LV end-diastolic diameter ratio >1.0.
    2. Cardiac injury or heart failure biomarker above the local upper limit of normal, including cardiac troponin, BNP, or NT-proBNP.

  • Elevated risk of early death/hemodynamic collapse, indicated by at least one of the following high-risk features: Systolic blood pressure ≤110 mmHg, Heart rate ≥100 beats/min, Oxygen saturation (SpO₂) <90% (respiratory rate >20 breaths/min or arterial partial pressure of oxygen [PaO₂] <60 mmHg).

  • Signed informed consent

Exclusion Criteria:

  • High-risk PTE with hemodynamic instability, including cardiac arrest, obstructive shock, or persistent hypotension defined as systolic blood pressure <90 mmHg or a decrease of ≥40 mmHg from baseline lasting at least 15 minutes, after excluding hypotension caused by new-onset arrhythmia, hypovolemia, or sepsis.

  • Intermediate-low-risk PTE, defined as hemodynamically stable PE with only one of the following findings: right ventricular dysfunction on imaging or elevated cardiac biomarkers.

  • Low-risk PTE, defined as hemodynamically stable PTE without right ventricular dysfunction and without elevated cardiac injury or heart failure biomarkers.

  • Any contraindication to systemic thrombolysis, including:

    1. Known hypersensitivity to alteplase, gentamicin, heparin, low-molecular-weight heparin, or any component of the study treatment;
    2. Active bleeding or high risk of bleeding;
    3. Known or suspected intracranial hemorrhage;
    4. Suspected subarachnoid hemorrhage or aneurysmal subarachnoid hemorrhage;
    5. Significant bleeding disorder within the previous 6 months;
    6. Known bleeding diathesis;
    7. Acute ischemic stroke or transient ischemic attack within the previous 6 months;
    8. Ophthalmic surgery within the previous 3 months, or abdominal, cardiac, thoracic, vascular, or orthopedic surgery or trauma within the previous 3 months;
    9. History of central nervous system disease or trauma, including tumor, aneurysm, head trauma, intracranial surgery, or spinal surgery;
    10. Platelet count <100 × 10^9/L;
    11. International normalized ratio (INR) >1.3;
    12. Current effective oral anticoagulant treatment;
    13. Traumatic cardiopulmonary resuscitation;
    14. Infective endocarditis or pericarditis;
    15. Acute pancreatitis;
    16. Noncompressible vascular puncture;
    17. Severe uncontrolled hypertension, with systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg;
    18. Any other condition considered by the investigator to confer a high bleeding risk;
    19. Severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varices, or active hepatitis;
    20. Gastrointestinal ulcer, esophageal varices, arterial aneurysm, or arteriovenous malformation within the previous 3 months;
    21. Tumor with bleeding tendency;
    22. Pregnancy or within 1 week postpartum;
    23. Diabetes with hemorrhagic retinopathy;

  • Body weight ≤40 kg.

  • Thrombolytic treatment within 30 days before randomization for the current episode of acute PE, including systemic or catheter-directed thrombolysis.

  • Catheter-directed mechanical thrombectomy or surgical pulmonary embolectomy before randomization for the current episode of acute PE.

  • Use of any direct oral anticoagulant within 30 days before randomization.

  • Current dual antiplatelet therapy.

  • Current participation in another interventional clinical trial.

  • Women of childbearing potential who are unwilling to use effective contraception or abstinence during the study.

  • Any other disease or condition that, in the investigator's judgment, would increase treatment risk.

  • Life expectancy <3 months or inability to complete 3-month follow-up.

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：单身的

武器和干预

参与者组/臂
干预/治疗
有源比较器：Reduced-Dose Alteplase and Standard Anticoagulation

Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) and reduced-dose alteplase [25 mg continuous intravenous infusion for 2 hours]
药品：Alteplase

Alteplase 25 mg will be administered by continuous intravenous infusion over 2 hours

药品：Standard Anticoagulation

Standard anticoagulation will consist of LMWH or UFH administered according to current guideline recommendations for at least 5 days
有源比较器：Standard Anticoagulation

Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH)
药品：Standard Anticoagulation

Standard anticoagulation will consist of LMWH or UFH administered according to current guideline recommendations for at least 5 days

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
大体时间：Between baseline and 48 hours
Between baseline and 48 hours

次要结果测量

结果测量
措施说明
大体时间
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
大体时间：Between baseline and 7 days
Between baseline and 7 days
Clinical Deterioration
大体时间：7 days
7 days
PE-Related Death
大体时间：7 days

Death caused by pulmonary embolism (PE)
7 days
All cause Death
大体时间：7 days
7 days
Recurrent PE
大体时间：7 days
7 days
Persistent Dyspnea
大体时间：6 months

Persistent Dyspnea Assessed by the Medical Research Council (MRC) Dyspnea Scale
6 months
Functional outcome
大体时间：6 months

Functional status will be assessed using the Post-Venous Thromboembolism Functional Status (PVFS) Scale, which measures limitations in usual activities and daily functioning after venous thromboembolism. The scale ranges from grade 0 (no functional limitations) to grade 4 (severe functional limitations requiring assistance with activities of daily living). Higher grades indicate greater functional impairment. Grade D indicates death before the scheduled assessment.
6 months
Persistent Right Ventricular Dysfunction
大体时间：6 months

Persistent right ventricular dysfunction is defined as an intermediate or high probability of pulmonary hypertension on echocardiography according to the European Society of Cardiology (ESC) criteria.
6 months
Chronic thromboembolic pulmonary disease (CTEPD) and/or Chronic thromboembolic pulmonary hypertension (CTEPH)
大体时间：12 months
12 months
Major bleeding
大体时间：30 days

Major bleeding will be defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria as fatal bleeding, symptomatic bleeding in a critical area or organ, a decrease in hemoglobin of ≥2 g/dL, or transfusion of ≥2 units of whole blood or red blood cells. The number of participants experiencing major bleeding will be recorded
30 days
Clinically relevant non-major bleeding
大体时间：30 days

Clinically relevant non-major bleeding will be defined according to ISTH criteria as bleeding that does not meet the criteria for major bleeding but requires medical intervention, leads to hospitalization or an increased level of care, or prompts a face-to-face evaluation by a healthcare professional. The number of participants experiencing clinically relevant non-major bleeding will be recorded.
30 days
Minor bleeding
大体时间：30 days

Minor bleeding will be defined as any overt bleeding event that does not meet the criteria for major bleeding or clinically relevant non-major bleeding and does not require medical attention. The number of participants experiencing minor bleeding will be recorded.
30 days

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

China National Center for Cardiovascular Diseases

调查人员

  • 首席研究员：Changming Xiong, Prof.、Chinese Academy of Medical Sciences, Fuwai Hospital
  • 首席研究员：Zhenguo Zhai, Prof.、China-Japan Friendship Hospital

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 (估计的)

2026年11月1日

初级完成 (估计的)

2028年12月31日

研究完成 (估计的)

2029年12月31日

研究注册日期

首次提交

2026年10月15日

首先提交符合 QC 标准的

2026年11月2日

首次发布 (实际的)

2026年11月4日

研究记录更新

最后更新发布 (实际的)

2026年11月4日

上次提交的符合 QC 标准的更新

2026年11月2日

最后验证

2026年10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

  • 2026ZD0556203-02
  • 2026ZD0556203 (其他赠款/资助编号：Noncommunicable Chronic Diseases-National Science and Technology Major Project)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

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

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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