Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

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

2. November 2026 aktualisiert von: 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.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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)

Studientyp

Interventionell

Einschreibung (Geschätzt)

270

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

  • Name: Changming Xiong, Prof.
  • Telefonnummer: (+86)010-88396798
  • E-Mail: xiongcmfw@163.com

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 75 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Single

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Aktiver Komparator: 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]
Arzneimittel: Alteplase

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

Arzneimittel: Standard Anticoagulation

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

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

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

Was misst die Studie?

Primäre Ergebnismessungen

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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Zeitfenster: Between baseline and 7 days
Between baseline and 7 days
Clinical Deterioration
Zeitfenster: 7 days
7 days
PE-Related Death
Zeitfenster: 7 days

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

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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

China National Center for Cardiovascular Diseases

Ermittler

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

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. November 2026

Primärer Abschluss (Geschätzt)

31. Dezember 2028

Studienabschluss (Geschätzt)

31. Dezember 2029

Studienanmeldedaten

Zuerst eingereicht

15. Oktober 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

2. November 2026

Zuerst gepostet (Tatsächlich)

4. November 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

4. November 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

2. November 2026

Zuletzt verifiziert

1. Oktober 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • 2026ZD0556203-02
  • 2026ZD0556203 (Andere Zuschuss-/Finanzierungsnummer: Noncommunicable Chronic Diseases-National Science and Technology Major Project)

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Abonnieren