Reduced-Dose Thrombolysis in Intermediate-Risk Pulmonary Embolism With High-Risk Features (REDUCTION)
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.
Обзор исследования
Статус
Статус
Условия
Условия
Вмешательство/лечение
Вмешательство/лечение
Подробное описание
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)
Тип исследования
Тип исследования
Регистрация (Оцененный)
Регистрация
Фаза
Фаза
- Фаза 3
Контакты и местонахождение
Контакты исследования
Контакты исследования
- Имя: Changming Xiong, Prof.
- Номер телефона: (+86)010-88396798
- Электронная почта: xiongcmfw@163.com
Места учебы
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Beijing, Китай, 100037
- Chinese Academy of Medical Sciences, Fuwai Hospital
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Контакт:
- Changming Xiong, Prof.
- Номер телефона: 010-88396798
- Электронная почта: xiongcmfw@163.com
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Beijing Municipality
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Beijing, Beijing Municipality, Китай, 100029
- China-Japan Friendship Hospital
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Контакт:
- Zhenguo Zhai
- Номер телефона: 010-84205566
- Электронная почта: zhaizhenguo2011@126.com
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Beijing, Beijing Municipality, Китай, 100730
- Peking Union Medical College Hospital
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Контакт:
- Juhong Shi, Prof.
- Номер телефона: 010-69156114
- Электронная почта: shijh@pumch.cn
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Beijing, Beijing Municipality, Китай, 100029
- Beijing Anzhen Hospital, Capital Medical University
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Контакт:
- Jun Wan, Prof.
- Номер телефона: 010-64412431
- Электронная почта: blueswan2013@yahoo.com
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Beijing, Beijing Municipality, Китай, 100020
- Beijing ChaoYang Hospital.Capital Medical University
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Контакт:
- Yuanhua Yang, Prof.
- Номер телефона: 010-85231777
- Электронная почта: yyh1031@sina.com
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Guangdong
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Guangzhou, Guangdong, Китай, 510120
- Guangdong Provincial Hospital of Chinese Medicine
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Контакт:
- Yinji Xu, Prof.
- Номер телефона: 020-81887233
- Электронная почта: xuyinji@163.com
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Guangzhou, Guangdong, Китай, 510120
- The First Affiliated Hospital of Guangzhou Medical University / Guangzhou Institute of Respiratory Health (National Clinical Research Center for Respiratory Disease)
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Контакт:
- Nuofu Zhang, Prof.
- Номер телефона: 020-83062114
- Электронная почта: nfzhanggird@163.com
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Shenzhen, Guangdong, Китай, 518116
- Longgang Central Hospital of Shenzhen
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Контакт:
- Siliang Xu, Prof.
- Номер телефона: 0755-84806933
- Электронная почта: 420814562@qq.com
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Hebei
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Zhangjiakou, Hebei, Китай, 075000
- The First Affiliated Hospital of Hebei North University
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Контакт:
- Baoli Xiang, Prof.
- Номер телефона: 0313-8043555
- Электронная почта: 15530396731@163.com
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Henan
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Xinxiang, Henan, Китай, 453400
- HeNan Honliv Hospital
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Контакт:
- Lei Yang, Prof.
- Номер телефона: 0373-8882288
- Электронная почта: 61194255@qq.com
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Zhengzhou, Henan, Китай, 450052
- The First Affiliated Hospital of Zhengzhou University
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Контакт:
- Zhe Cheng, Prof.
- Номер телефона: 0371-66913114
- Электронная почта: chengzhehi@126.com
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Zhengzhou, Henan, Китай, 450003
- Henan Provincial People's Hospital
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Контакт:
- Yong Qi, Prof.
- Номер телефона: 0371-65580014
- Электронная почта: srmyy123@163.com
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Hubei
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Wuhan, Hubei, Китай, 430015
- Wuhan Sixth Hospital (Affiliated Hospital of Jianghan University)
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Контакт:
- Fajiu Li, Prof.
- Номер телефона: 027-82426502
- Электронная почта: 80670519@qq.com
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Inner Mongolia
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Baotou, Inner Mongolia, Китай, 014010
- Inner Mongolia Baogang Hospital
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Контакт:
- Hongjun Tian, Prof.
- Номер телефона: 0472-5992811
- Электронная почта: 1139717960@qq.com
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Tongliao, Inner Mongolia, Китай, 028000
- NMG Keerqin District Hosp.
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Контакт:
- Xili Wang, Prof.
- Номер телефона: 0475-8232510
- Электронная почта: 861004223@qq.com
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Jiangsu
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Changzhou, Jiangsu, Китай, 213003
- The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University
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Контакт:
- Qian Zhang, Prof.
- Номер телефона: 0519-81099988
- Электронная почта: kezhang0601@163.com
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Nanjing, Jiangsu, Китай, 210006
- Nanjing First Hospital
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Контакт:
- He Xu, Prof.
- Номер телефона: 025-52271000
- Электронная почта: hexunj@163.com
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Liaoning
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Shenyang, Liaoning, Китай, 110024
- Central Hospital Affiliated to Shenyang Medical College
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Контакт:
- Shuyue Xia, Prof.
- Номер телефона: 024-85715200
- Электронная почта: syx262@126.com
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Shenyang, Liaoning, Китай, 110003
- General Hospital of Northern Theater Command
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Контакт:
- Liang Shi, Prof.
- Номер телефона: 024-28886666
- Электронная почта: 13309889463@163.com
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Ningxia
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Yinchuan, Ningxia, Китай, 750004
- Ningxia Medical University General Hospital
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Контакт:
- Juan Chen, Prof.
- Номер телефона: 0951-6744457
- Электронная почта: chenjuan7419@163.com
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Shandong
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Jinan, Shandong, Китай, 250021
- Shandong Provincial Hospital
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Контакт:
- Ling Zhu, Prof.
- Номер телефона: 0531-87938911
- Электронная почта: zhuling7103@163.com
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Linyi, Shandong, Китай, 276000
- Linyi People's Hospital
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Контакт:
- Le Kang, Prof.
- Номер телефона: 0539-8616398
- Электронная почта: 593119267@qq.com
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Китай, 200120
- Shanghai East Hospital, School of Medicine, Tongji University
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Контакт:
- Yingqun Ji, Prof.
- Номер телефона: 021-38804518
- Электронная почта: jiyingqun@163.com
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Sichuan
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Chengdu, Sichuan, Китай, 610041
- West China Hospital, Sichuan University
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Контакт:
- Maojun Wang, Prof.
- Номер телефона: 028-85422114
- Электронная почта: wmmyun@hotmail.com
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Китай, 300052
- Tianjin Medical University General Hospital
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Контакт:
- Lixia Dong, Prof.
- Номер телефона: 022-96580
- Электронная почта: 18355193818@163.COM
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Tianjin, Tianjin Municipality, Китай, 300222
- Tianjin Chest Hospital
-
Контакт:
- Songtao Gu
- Номер телефона: 022-88185111
- Электронная почта: gusongtaodoctor@126.com
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Критерии участия
Критерии приемлемости
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
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Age 18 to 75 years
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Objectively confirmed acute pulmonary thromboembolism (PTE) with symptom onset within 14 days, based on at least one of the following:
- Ventilation/perfusion lung scan showing at least one segmental or larger mismatched perfusion defect;
- Computed tomography pulmonary angiography (CTPA) or pulmonary angiography showing a filling defect or abrupt obstruction in a segmental or more proximal pulmonary artery.
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Intermediate-high-risk PTE, with both of the following:
- 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.
- Cardiac injury or heart failure biomarker above the local upper limit of normal, including cardiac troponin, BNP, or NT-proBNP.
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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).
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Signed informed consent
Exclusion Criteria:
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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.
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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.
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Low-risk PTE, defined as hemodynamically stable PTE without right ventricular dysfunction and without elevated cardiac injury or heart failure biomarkers.
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Any contraindication to systemic thrombolysis, including:
- Known hypersensitivity to alteplase, gentamicin, heparin, low-molecular-weight heparin, or any component of the study treatment;
- Active bleeding or high risk of bleeding;
- Known or suspected intracranial hemorrhage;
- Suspected subarachnoid hemorrhage or aneurysmal subarachnoid hemorrhage;
- Significant bleeding disorder within the previous 6 months;
- Known bleeding diathesis;
- Acute ischemic stroke or transient ischemic attack within the previous 6 months;
- Ophthalmic surgery within the previous 3 months, or abdominal, cardiac, thoracic, vascular, or orthopedic surgery or trauma within the previous 3 months;
- History of central nervous system disease or trauma, including tumor, aneurysm, head trauma, intracranial surgery, or spinal surgery;
- Platelet count <100 × 10^9/L;
- International normalized ratio (INR) >1.3;
- Current effective oral anticoagulant treatment;
- Traumatic cardiopulmonary resuscitation;
- Infective endocarditis or pericarditis;
- Acute pancreatitis;
- Noncompressible vascular puncture;
- Severe uncontrolled hypertension, with systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg;
- Any other condition considered by the investigator to confer a high bleeding risk;
- Severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varices, or active hepatitis;
- Gastrointestinal ulcer, esophageal varices, arterial aneurysm, or arteriovenous malformation within the previous 3 months;
- Tumor with bleeding tendency;
- Pregnancy or within 1 week postpartum;
- Diabetes with hemorrhagic retinopathy;
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Body weight ≤40 kg.
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Thrombolytic treatment within 30 days before randomization for the current episode of acute PE, including systemic or catheter-directed thrombolysis.
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Catheter-directed mechanical thrombectomy or surgical pulmonary embolectomy before randomization for the current episode of acute PE.
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Use of any direct oral anticoagulant within 30 days before randomization.
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Current dual antiplatelet therapy.
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Current participation in another interventional clinical trial.
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Women of childbearing potential who are unwilling to use effective contraception or abstinence during the study.
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Any other disease or condition that, in the investigator's judgment, would increase treatment risk.
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Life expectancy <3 months or inability to complete 3-month follow-up.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Одинокий
Количество рук
Оружие и интервенции
Группа участников / АрмияГруппа участников / Армия |
Вмешательство/лечениеВмешательство/лечение |
|---|---|
|
Активный компаратор: 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] |
Alteplase 25 mg will be administered by continuous intravenous infusion over 2 hours Standard anticoagulation will consist of LMWH or UFH administered according to current guideline recommendations for at least 5 days |
|
Активный компаратор: Standard Anticoagulation
Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) |
Standard anticoagulation will consist of LMWH or UFH administered according to current guideline recommendations for at least 5 days |
Что измеряет исследование?
Первичные показатели результатов
Первичные показатели результатов
Мера результата |
Временное ограничение |
|---|---|
|
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Временное ограничение: Between baseline and 48 hours
|
Between baseline and 48 hours
|
Вторичные показатели результатов
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Временное ограничение: Between baseline and 7 days
|
Between baseline and 7 days
|
|
|
Clinical Deterioration
Временное ограничение: 7 days
|
7 days
|
|
|
PE-Related Death
Временное ограничение: 7 days
|
Death caused by pulmonary embolism (PE) |
7 days
|
|
All cause Death
Временное ограничение: 7 days
|
7 days
|
|
|
Recurrent PE
Временное ограничение: 7 days
|
7 days
|
|
|
Persistent Dyspnea
Временное ограничение: 6 months
|
Persistent Dyspnea Assessed by the Medical Research Council (MRC) Dyspnea Scale |
6 months
|
|
Functional outcome
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 12 months
|
12 months
|
|
|
Major bleeding
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
|
Соавторы и исследователи
Спонсор
Спонсор
Следователи
Следователи
- Главный следователь: Changming Xiong, Prof., Chinese Academy of Medical Sciences, Fuwai Hospital
- Главный следователь: Zhenguo Zhai, Prof., China-Japan Friendship Hospital
Публикации и полезные ссылки
Общие публикации
- Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; "MOPETT" Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027. Epub 2012 Oct 24.
- Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
- Wang C, Zhai Z, Yang Y, Wu Q, Cheng Z, Liang L, Dai H, Huang K, Lu W, Zhang Z, Cheng X, Shen YH; China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010 Feb;137(2):254-62. doi: 10.1378/chest.09-0765. Epub 2009 Sep 9.
- Sanchez O, Charles-Nelson A, Ageno W, Barco S, Binder H, Chatellier G, Duerschmied D, Empen K, Ferreira M, Girard P, Huisman MV, Jimenez D, Katsahian S, Kozak M, Lankeit M, Meneveau N, Pruszczyk P, Petris A, Righini M, Rosenkranz S, Schellong S, Stefanovic B, Verhamme P, de Wit K, Vicaut E, Zirlik A, Konstantinides SV, Meyer G; PEITHO-3 Investigators. Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial. Thromb Haemost. 2022 May;122(5):857-866. doi: 10.1055/a-1653-4699. Epub 2021 Oct 31.
- Liu L, Li C, Shi L, Ma D, Zhang Z, Bao H, Li C, Li L, Wang M, Ma Z, Zhang J. Efficacy and safety of low-dose thrombolysis in acute intermediate-high risk pulmonary thromboembolism complicated by PaO2/FiO2 < 300. Front Med (Lausanne). 2026 Jul 9;13:1849541. doi: 10.3389/fmed.2026.1849541. eCollection 2026.
- Yilmaz ES, Uzun O. Low-dose thrombolysis for submassive pulmonary embolism. J Investig Med. 2021 Dec;69(8):1439-1446. doi: 10.1136/jim-2021-001816. Epub 2021 Jun 7.
- Zhang LY, Gao BA, Jin Z, Xiang GM, Gong Z, Zhang TT, Lu HF, Wang YQ, Gong Y, Lu C, Huang WL. Clinical efficacy of low dose recombinant tissue-type plasminogen activator for the treatment of acute intermediate-risk pulmonary embolism. Saudi Med J. 2018 Nov;39(11):1090-1095. doi: 10.15537/smj.2018.11.22717.
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Начало исследования
Первичное завершение (Оцененный)
Первичное завершение
Завершение исследования (Оцененный)
Завершение исследования
Даты регистрации исследования
Первый отправленный
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Первый опубликованный
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее опубликованное обновление
Последнее отправленное обновление, отвечающее критериям контроля качества
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Сосудистые заболевания
- Сердечно-сосудистые заболевания
- Заболевания дыхательных путей
- Легочные заболевания
- Эмболия и тромбоз
- Эмболия
- Легочная эмболия
- Аминокислоты, пептиды и белки
- Белки
- Биологические факторы
- Гидролазы
- Ферменты
- Ферменты и коэнзименты
- Белки крови
- Эндопептидазы
- Пептидные гидролазы
- Сериновые эндопептидазы
- Сериновые протеазы
- Активаторы плазминогена
- Факторы коагуляции крови
- Тканевой активатор плазминогена
Другие идентификационные номера исследования
Другие идентификационные номера исследования
- 2026ZD0556203-02
- 2026ZD0556203 (Другой номер гранта/финансирования: Noncommunicable Chronic Diseases-National Science and Technology Major Project)
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .