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

2. listopadu 2026 aktualizováno: 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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)

Typ studie

Intervenční

Zápis (Odhadovaný)

270

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

  • Jméno: Changming Xiong, Prof.
  • Telefonní číslo: (+86)010-88396798
  • E-mail: xiongcmfw@163.com

Studijní místa

  • Čína
      • Beijing, Čína, 100037
        • Chinese Academy of Medical Sciences, Fuwai Hospital
        • Kontakt:
    • Beijing Municipality
      • Beijing, Beijing Municipality, Čína, 100029
        • China-Japan Friendship Hospital
        • Kontakt:
      • Beijing, Beijing Municipality, Čína, 100730
        • Peking Union Medical College Hospital
        • Kontakt:
          • Juhong Shi, Prof.
          • Telefonní číslo: 010-69156114
          • E-mail: shijh@pumch.cn
      • Beijing, Beijing Municipality, Čína, 100029
        • Beijing Anzhen Hospital, Capital Medical University
        • Kontakt:
      • Beijing, Beijing Municipality, Čína, 100020
        • Beijing ChaoYang Hospital.Capital Medical University
        • Kontakt:
    • Guangdong
      • Guangzhou, Guangdong, Čína, 510120
        • Guangdong Provincial Hospital of Chinese Medicine
        • Kontakt:
      • Guangzhou, Guangdong, Čína, 510120
        • The First Affiliated Hospital of Guangzhou Medical University / Guangzhou Institute of Respiratory Health (National Clinical Research Center for Respiratory Disease)
        • Kontakt:
      • Shenzhen, Guangdong, Čína, 518116
        • Longgang Central Hospital of Shenzhen
        • Kontakt:
    • Hebei
      • Zhangjiakou, Hebei, Čína, 075000
        • The First Affiliated Hospital of Hebei North University
        • Kontakt:
    • Henan
      • Xinxiang, Henan, Čína, 453400
        • HeNan Honliv Hospital
        • Kontakt:
      • Zhengzhou, Henan, Čína, 450052
        • The First Affiliated Hospital of Zhengzhou University
        • Kontakt:
      • Zhengzhou, Henan, Čína, 450003
        • Henan Provincial People's Hospital
        • Kontakt:
    • Hubei
      • Wuhan, Hubei, Čína, 430015
        • Wuhan Sixth Hospital (Affiliated Hospital of Jianghan University)
        • Kontakt:
    • Inner Mongolia
      • Baotou, Inner Mongolia, Čína, 014010
        • Inner Mongolia Baogang Hospital
        • Kontakt:
      • Tongliao, Inner Mongolia, Čína, 028000
        • NMG Keerqin District Hosp.
        • Kontakt:
    • Jiangsu
      • Changzhou, Jiangsu, Čína, 213003
        • The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University
        • Kontakt:
      • Nanjing, Jiangsu, Čína, 210006
        • Nanjing First Hospital
        • Kontakt:
          • He Xu, Prof.
          • Telefonní číslo: 025-52271000
          • E-mail: hexunj@163.com
    • Liaoning
      • Shenyang, Liaoning, Čína, 110024
        • Central Hospital Affiliated to Shenyang Medical College
        • Kontakt:
          • Shuyue Xia, Prof.
          • Telefonní číslo: 024-85715200
          • E-mail: syx262@126.com
      • Shenyang, Liaoning, Čína, 110003
        • General Hospital of Northern Theater Command
        • Kontakt:
    • Ningxia
      • Yinchuan, Ningxia, Čína, 750004
        • Ningxia Medical University General Hospital
        • Kontakt:
    • Shandong
      • Jinan, Shandong, Čína, 250021
        • Shandong Provincial Hospital
        • Kontakt:
      • Linyi, Shandong, Čína, 276000
        • Linyi People's Hospital
        • Kontakt:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Čína, 200120
        • Shanghai East Hospital, School of Medicine, Tongji University
        • Kontakt:
    • Sichuan
      • Chengdu, Sichuan, Čína, 610041
        • West China Hospital, Sichuan University
        • Kontakt:
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, Čína, 300052
        • Tianjin Medical University General Hospital
        • Kontakt:
      • Tianjin, Tianjin Municipality, Čína, 300222

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 75 let (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Singl

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Aktivní komparátor: 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]
Lék: Alteplase

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

Lék: Standard Anticoagulation

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

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

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

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Časové okno
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Časové okno: Between baseline and 48 hours
Between baseline and 48 hours

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Časové okno: Between baseline and 7 days
Between baseline and 7 days
Clinical Deterioration
Časové okno: 7 days
7 days
PE-Related Death
Časové okno: 7 days

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

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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

China National Center for Cardiovascular Diseases

Vyšetřovatelé

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

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. listopadu 2026

Primární dokončení (Odhadovaný)

31. prosince 2028

Dokončení studie (Odhadovaný)

31. prosince 2029

Termíny zápisu do studia

První předloženo

15. října 2026

První předloženo, které splnilo kritéria kontroly kvality

2. listopadu 2026

První zveřejněno (Aktuální)

4. listopadu 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

4. listopadu 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

2. listopadu 2026

Naposledy ověřeno

1. října 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • 2026ZD0556203-02
  • 2026ZD0556203 (Jiné číslo grantu/financování: Noncommunicable Chronic Diseases-National Science and Technology Major Project)

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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