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Not yet recruitingNCT07917078REDUCTIONUpdated Nov 4, 2026

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

A Phase 3 interventional study of Alteplase and Standard Anticoagulation in Pulmonary Embolism, sponsored by China National Center for Cardiovascular Diseases. Not yet recruiting at 26 sites in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-11-04.

Sponsored by China National Center for Cardiovascular Diseases · Phase 3, Interventional, and Treatment

Updated Nov 4, 2026Newly registeredGo to Updates ↓
Phase
Phase 3
Study type
Interventional
Enrollment
270
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

Read the 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)

02

Conditions studied

  • Pulmonary Embolism

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Keywords

  • Acute intermediate-high risk pulmonary embolism
  • Thrombolysis
03

In context

Pulmonary Embolism

756 studies on the registry are indexed under Pulmonary Embolism; 159 are open to participants now.

This study's planned enrollment of 270 is above the median of 155 across 390 interventional studies indexed under Pulmonary Embolism.

Browse Pulmonary Embolism studies →

Lead sponsor

China National Center for Cardiovascular Diseases is the lead sponsor of 266 studies on the registry; 138 are open to participants now.

Browse China National Center for Cardiovascular Diseases studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
270 participants (estimated)

Study arms

  • 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 · Drug: Standard Anticoagulation

  • Active comparator
    Standard Anticoagulation

    Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH)

    Drug: Standard Anticoagulation

Interventions

  • DrugAlteplase

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

  • DrugStandard Anticoagulation

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

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. Clinical Deterioration

    Time frame: 7 days

  3. PE-Related Death

    Death caused by pulmonary embolism (PE)

    Time frame: 7 days

  4. All cause Death

    Time frame: 7 days

  5. Recurrent PE

    Time frame: 7 days

  6. Persistent Dyspnea

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

    Time frame: 6 months

  7. Functional outcome

    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.

    Time frame: 6 months

  8. Persistent Right Ventricular Dysfunction

    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.

    Time frame: 6 months

  9. Chronic thromboembolic pulmonary disease (CTEPD) and/or Chronic thromboembolic pulmonary hypertension (CTEPH)

    Time frame: 12 months

  10. Major bleeding

    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

    Time frame: 30 days

  11. Clinically relevant non-major bleeding

    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.

    Time frame: 30 days

  12. Minor bleeding

    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.

    Time frame: 30 days

07

Study locations

26 sites
08

References and documents

Publications

  • Liu L, Li C, Shi L, Ma D, Zhang Z, Bao H, Li C, Li L, Wang M, Ma Z, Zhang J. Efficacy and safety of low-dose thrombolysis in acute intermediate-high risk pulmonary thromboembolism complicated by PaO2/FiO2 < 300. Front Med (Lausanne). 2026 Jul 9;13:1849541. doi: 10.3389/fmed.2026.1849541. eCollection 2026. PubMed 42494448 ↗
  • Sanchez O, Charles-Nelson A, Ageno W, Barco S, Binder H, Chatellier G, Duerschmied D, Empen K, Ferreira M, Girard P, Huisman MV, Jimenez D, Katsahian S, Kozak M, Lankeit M, Meneveau N, Pruszczyk P, Petris A, Righini M, Rosenkranz S, Schellong S, Stefanovic B, Verhamme P, de Wit K, Vicaut E, Zirlik A, Konstantinides SV, Meyer G; PEITHO-3 Investigators. Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial. Thromb Haemost. 2022 May;122(5):857-866. doi: 10.1055/a-1653-4699. Epub 2021 Oct 31. PubMed 34560806 ↗
  • Yilmaz ES, Uzun O. Low-dose thrombolysis for submassive pulmonary embolism. J Investig Med. 2021 Dec;69(8):1439-1446. doi: 10.1136/jim-2021-001816. Epub 2021 Jun 7. PubMed 34099544 ↗
  • Zhang LY, Gao BA, Jin Z, Xiang GM, Gong Z, Zhang TT, Lu HF, Wang YQ, Gong Y, Lu C, Huang WL. Clinical efficacy of low dose recombinant tissue-type plasminogen activator for the treatment of acute intermediate-risk pulmonary embolism. Saudi Med J. 2018 Nov;39(11):1090-1095. doi: 10.15537/smj.2018.11.22717. PubMed 30397707 ↗
  • Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; "MOPETT" Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027. Epub 2012 Oct 24. PubMed 23102885 ↗
  • Wang C, Zhai Z, Yang Y, Wu Q, Cheng Z, Liang L, Dai H, Huang K, Lu W, Zhang Z, Cheng X, Shen YH; China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010 Feb;137(2):254-62. doi: 10.1378/chest.09-0765. Epub 2009 Sep 9. PubMed 19741062 ↗
  • Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097. PubMed 24716681 ↗

Individual participant data

Plan to share: No

09

Updates

1 registry update since Sep 25, 2026
Registered
First appeared on the registry. No changes since
Nov 4, 2026
Show all 1 update
  1. Nov 4, 2026
    First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07917078
Lead sponsor
China National Center for Cardiovascular Diseases
Responsible party
Sponsor
First posted
Nov 4, 2026
Start date
Nov 1, 2026 (estimated)
Primary completion
Dec 31, 2028 (estimated)
Completion
Dec 31, 2029 (estimated)
Last update
Nov 4, 2026

Study contacts

Changming Xiong, Prof.
Contact
xiongcmfw@163.com
(+86)010-88396798
Changming Xiong, Prof.
principal investigator · Chinese Academy of Medical Sciences, Fuwai Hospital
Zhenguo Zhai, Prof.
principal investigator · China-Japan Friendship Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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