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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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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)

Tipo di studio

Interventistico

Iscrizione (Stimato)

270

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

  • Nome: Changming Xiong, Prof.
  • Numero di telefono: (+86)010-88396798
  • Email: xiongcmfw@163.com

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Separare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: 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

Comparatore attivo: 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

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Lasso di tempo: Between baseline and 48 hours
Between baseline and 48 hours

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Lasso di tempo: Between baseline and 7 days
Between baseline and 7 days
Clinical Deterioration
Lasso di tempo: 7 days
7 days
PE-Related Death
Lasso di tempo: 7 days

Death caused by pulmonary embolism (PE)

7 days
All cause Death
Lasso di tempo: 7 days
7 days
Recurrent PE
Lasso di tempo: 7 days
7 days
Persistent Dyspnea
Lasso di tempo: 6 months

Persistent Dyspnea Assessed by the Medical Research Council (MRC) Dyspnea Scale

6 months
Functional outcome
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 12 months
12 months
Major bleeding
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 novembre 2026

Completamento primario (Stimato)

31 dicembre 2028

Completamento dello studio (Stimato)

31 dicembre 2029

Date di iscrizione allo studio

Primo inviato

15 ottobre 2026

Primo inviato che soddisfa i criteri di controllo qualità

2 novembre 2026

Primo Inserito (Effettivo)

4 novembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

4 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

2 novembre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Altri numeri di identificazione dello studio

  • 2026ZD0556203-02
  • 2026ZD0556203 (Altro numero di sovvenzione/finanziamento: Noncommunicable Chronic Diseases-National Science and Technology Major Project)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .