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

November 2, 2026 updated by: 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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)

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Changming Xiong, Prof.
  • Phone Number: (+86)010-88396798
  • Email: xiongcmfw@163.com

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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]
Drug: Alteplase

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

Drug: Standard Anticoagulation

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

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Time Frame: Between baseline and 48 hours
Between baseline and 48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Time Frame: Between baseline and 7 days
Between baseline and 7 days
Clinical Deterioration
Time Frame: 7 days
7 days
PE-Related Death
Time Frame: 7 days

Death caused by pulmonary embolism (PE)
7 days
All cause Death
Time Frame: 7 days
7 days
Recurrent PE
Time Frame: 7 days
7 days
Persistent Dyspnea
Time Frame: 6 months

Persistent Dyspnea Assessed by the Medical Research Council (MRC) Dyspnea Scale
6 months
Functional outcome
Time Frame: 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
Time Frame: 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)
Time Frame: 12 months
12 months
Major bleeding
Time Frame: 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
Time Frame: 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
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

China National Center for Cardiovascular Diseases

Investigators

  • Principal Investigator: Changming Xiong, Prof., Chinese Academy of Medical Sciences, Fuwai Hospital
  • Principal Investigator: Zhenguo Zhai, Prof., China-Japan Friendship Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

October 15, 2026

First Submitted That Met QC Criteria

November 2, 2026

First Posted (Actual)

November 4, 2026

Study Record Updates

Last Update Posted (Actual)

November 4, 2026

Last Update Submitted That Met QC Criteria

November 2, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026ZD0556203-02
  • 2026ZD0556203 (Other Grant/Funding Number: Noncommunicable Chronic Diseases-National Science and Technology Major Project)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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