Lower-dose alteplase for pulmonary embolism with higher-risk features

Who can take part

• 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:; Ventilation/perfusion lung scan showing at least one segmental or larger mismatched perfusion defect; 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:; 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; 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

Who cannot take part

• 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
• 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 other disease or condition that, in the investigator's judgment, would increase treatment risk
• Any contraindication to systemic thrombolysis, including:; Known hypersensitivity to alteplase, gentamicin, heparin, low-molecular-weight heparin, or any component of the study treatment; Active bleeding or high risk of bleeding; Known or suspected intracranial hemorrhage; Suspected subarachnoid hemorrhage or aneurysmal subarachnoid hemorrhage; Significant bleeding disorder within the previous 6 months; Known bleeding diathesis; Acute ischemic stroke or transient ischemic attack within the previous 6 months; Ophthalmic surgery within the previous 3 months, or abdominal, cardiac, thoracic, vascular, or orthopedic surgery or trauma within the previous 3 months; History of central nervous system disease or trauma, including tumor, aneurysm, head trauma, intracranial surgery, or spinal surgery; Platelet count <100 × 10\^9/L; International normalized ratio (INR) >1.3; Current effective oral anticoagulant treatment; Traumatic cardiopulmonary resuscitation; Infective endocarditis or pericarditis; Acute pancreatitis; Noncompressible vascular puncture; Severe uncontrolled hypertension, with systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg; Any other condition considered by the investigator to confer a high bleeding risk; Severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varices, or active hepatitis; Gastrointestinal ulcer, esophageal varices, arterial aneurysm, or arteriovenous malformation within the previous 3 months; Tumor with bleeding tendency; Pregnancy or within 1 week postpartum; Diabetes with hemorrhagic retinopathy
• Body weight ≤40 kg
• Current participation in another interventional clinical trial
• Women of childbearing potential who are unwilling to use effective contraception or abstinence during the study
• Life expectancy <3 months or inability to complete 3-month follow-up