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

2026년 11월 2일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

정황

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

중재적

등록 (추정된)

270

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Changming Xiong, Prof.
  • 전화번호: (+86)010-88396798
  • 이메일: xiongcmfw@163.com

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 하나의

무기와 개입

참가자 그룹 / 팔
개입 / 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

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

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

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

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

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 11월 1일

기본 완료 (추정된)

2028년 12월 31일

연구 완료 (추정된)

2029년 12월 31일

연구 등록 날짜

최초 제출

2026년 10월 15일

QC 기준을 충족하는 최초 제출

2026년 11월 2일

처음 게시됨 (실제)

2026년 11월 4일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 4일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 11월 2일

마지막으로 확인됨

2026년 10월 1일

추가 정보

이 연구와 관련된 용어

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

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아니요

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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. .