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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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)
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 3단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Changming Xiong, Prof.
- 전화번호: (+86)010-88396798
- 이메일: xiongcmfw@163.com
연구 장소
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Beijing, 중국, 100037
- Chinese Academy of Medical Sciences, Fuwai Hospital
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연락하다:
- Changming Xiong, Prof.
- 전화번호: 010-88396798
- 이메일: xiongcmfw@163.com
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Beijing Municipality
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Beijing, Beijing Municipality, 중국, 100029
- China-Japan Friendship Hospital
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연락하다:
- Zhenguo Zhai
- 전화번호: 010-84205566
- 이메일: zhaizhenguo2011@126.com
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Beijing, Beijing Municipality, 중국, 100730
- Peking Union Medical College Hospital
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연락하다:
- Juhong Shi, Prof.
- 전화번호: 010-69156114
- 이메일: shijh@pumch.cn
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Beijing, Beijing Municipality, 중국, 100029
- Beijing Anzhen Hospital, Capital Medical University
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연락하다:
- Jun Wan, Prof.
- 전화번호: 010-64412431
- 이메일: blueswan2013@yahoo.com
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Beijing, Beijing Municipality, 중국, 100020
- Beijing ChaoYang Hospital.Capital Medical University
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연락하다:
- Yuanhua Yang, Prof.
- 전화번호: 010-85231777
- 이메일: yyh1031@sina.com
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Guangdong
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Guangzhou, Guangdong, 중국, 510120
- Guangdong Provincial Hospital of Chinese Medicine
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연락하다:
- Yinji Xu, Prof.
- 전화번호: 020-81887233
- 이메일: xuyinji@163.com
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Guangzhou, Guangdong, 중국, 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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연락하다:
- Nuofu Zhang, Prof.
- 전화번호: 020-83062114
- 이메일: nfzhanggird@163.com
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Shenzhen, Guangdong, 중국, 518116
- Longgang Central Hospital of Shenzhen
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연락하다:
- Siliang Xu, Prof.
- 전화번호: 0755-84806933
- 이메일: 420814562@qq.com
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Hebei
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Zhangjiakou, Hebei, 중국, 075000
- The First Affiliated Hospital of Hebei North University
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연락하다:
- Baoli Xiang, Prof.
- 전화번호: 0313-8043555
- 이메일: 15530396731@163.com
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Henan
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Xinxiang, Henan, 중국, 453400
- HeNan Honliv Hospital
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연락하다:
- Lei Yang, Prof.
- 전화번호: 0373-8882288
- 이메일: 61194255@qq.com
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Zhengzhou, Henan, 중국, 450052
- The First Affiliated Hospital of Zhengzhou University
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연락하다:
- Zhe Cheng, Prof.
- 전화번호: 0371-66913114
- 이메일: chengzhehi@126.com
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Zhengzhou, Henan, 중국, 450003
- Henan Provincial People's Hospital
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연락하다:
- Yong Qi, Prof.
- 전화번호: 0371-65580014
- 이메일: srmyy123@163.com
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Hubei
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Wuhan, Hubei, 중국, 430015
- Wuhan Sixth Hospital (Affiliated Hospital of Jianghan University)
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연락하다:
- Fajiu Li, Prof.
- 전화번호: 027-82426502
- 이메일: 80670519@qq.com
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Inner Mongolia
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Baotou, Inner Mongolia, 중국, 014010
- Inner Mongolia Baogang Hospital
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연락하다:
- Hongjun Tian, Prof.
- 전화번호: 0472-5992811
- 이메일: 1139717960@qq.com
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Tongliao, Inner Mongolia, 중국, 028000
- NMG Keerqin District Hosp.
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연락하다:
- Xili Wang, Prof.
- 전화번호: 0475-8232510
- 이메일: 861004223@qq.com
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Jiangsu
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Changzhou, Jiangsu, 중국, 213003
- The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University
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연락하다:
- Qian Zhang, Prof.
- 전화번호: 0519-81099988
- 이메일: kezhang0601@163.com
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Nanjing, Jiangsu, 중국, 210006
- Nanjing First Hospital
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연락하다:
- He Xu, Prof.
- 전화번호: 025-52271000
- 이메일: hexunj@163.com
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Liaoning
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Shenyang, Liaoning, 중국, 110024
- Central Hospital Affiliated to Shenyang Medical College
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연락하다:
- Shuyue Xia, Prof.
- 전화번호: 024-85715200
- 이메일: syx262@126.com
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Shenyang, Liaoning, 중국, 110003
- General Hospital of Northern Theater Command
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연락하다:
- Liang Shi, Prof.
- 전화번호: 024-28886666
- 이메일: 13309889463@163.com
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Ningxia
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Yinchuan, Ningxia, 중국, 750004
- Ningxia Medical University General Hospital
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연락하다:
- Juan Chen, Prof.
- 전화번호: 0951-6744457
- 이메일: chenjuan7419@163.com
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Shandong
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Jinan, Shandong, 중국, 250021
- Shandong Provincial Hospital
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연락하다:
- Ling Zhu, Prof.
- 전화번호: 0531-87938911
- 이메일: zhuling7103@163.com
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Linyi, Shandong, 중국, 276000
- Linyi People's Hospital
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연락하다:
- Le Kang, Prof.
- 전화번호: 0539-8616398
- 이메일: 593119267@qq.com
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Shanghai Municipality
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Shanghai, Shanghai Municipality, 중국, 200120
- Shanghai East Hospital, School of Medicine, Tongji University
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연락하다:
- Yingqun Ji, Prof.
- 전화번호: 021-38804518
- 이메일: jiyingqun@163.com
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Sichuan
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Chengdu, Sichuan, 중국, 610041
- West China Hospital, Sichuan University
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연락하다:
- Maojun Wang, Prof.
- 전화번호: 028-85422114
- 이메일: wmmyun@hotmail.com
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Tianjin Municipality
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Tianjin, Tianjin Municipality, 중국, 300052
- Tianjin Medical University General Hospital
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연락하다:
- Lixia Dong, Prof.
- 전화번호: 022-96580
- 이메일: 18355193818@163.COM
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Tianjin, Tianjin Municipality, 중국, 300222
- Tianjin Chest Hospital
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연락하다:
- Songtao Gu
- 전화번호: 022-88185111
- 이메일: gusongtaodoctor@126.com
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
활성 비교기: 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 |
|
활성 비교기: 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 |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
기간 |
|---|---|
|
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
기간: Between baseline and 48 hours
|
Between baseline and 48 hours
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
기간: Between baseline and 7 days
|
Between baseline and 7 days
|
|
|
Clinical Deterioration
기간: 7 days
|
7 days
|
|
|
PE-Related Death
기간: 7 days
|
Death caused by pulmonary embolism (PE) |
7 days
|
|
All cause Death
기간: 7 days
|
7 days
|
|
|
Recurrent PE
기간: 7 days
|
7 days
|
|
|
Persistent Dyspnea
기간: 6 months
|
Persistent Dyspnea Assessed by the Medical Research Council (MRC) Dyspnea Scale |
6 months
|
|
Functional outcome
기간: 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
기간: 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)
기간: 12 months
|
12 months
|
|
|
Major bleeding
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
수사관
수사관
- 수석 연구원: Changming Xiong, Prof., Chinese Academy of Medical Sciences, Fuwai Hospital
- 수석 연구원: Zhenguo Zhai, Prof., China-Japan Friendship Hospital
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- 2026ZD0556203-02
- 2026ZD0556203 (기타 보조금/기금 번호: Noncommunicable Chronic Diseases-National Science and Technology Major Project)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .