Reduced-Dose Versus Full-Dose Alteplase for High-Risk Pulmonary Embolism

Inclusion Criteria: 1. Participant aged 18 years or older. 2. Acute pulmonary embolism verified by computed tomography pulmonary angiography or pulmonary angiography. In hemodynamically unstable participants unable to undergo immediate imaging, presumed pulmonary embolism may be diagnosed based on bedside echocardiographic findings consistent with acute right ventricular pressure overload and high clinical suspicion of pulmonary embolism, provided that alternative causes of hemodynamic instability have been reasonably excluded. In such cases, the treating clinician must have independently decided to initiate thrombolytic therapy irrespective of study participation, and confirmatory imaging demonstrating pulmonary embolism must be performed as soon as clinically feasible. 3. High risk for early death, defined by at least one of the following: 1. High-risk pulmonary embolism according to European Society of Cardiology criteria: * Cardiac arrest with return of spontaneous circulation; * Obstructive shock, defined as systolic blood pressure \<90 mmHg or use of vasopressors to maintain systolic blood pressure ≥90 mmHg despite adequate filling status, together with end-organ hypoperfusion such as elevated serum lactate \>2 mmol/L, altered mental status, or cold clammy skin; * Persistent hypotension, defined as systolic blood pressure \<90 mmHg or a drop in systolic blood pressure ≥40 mmHg for longer than 15 minutes, not caused by new-onset arrhythmia, hypovolemia, or sepsis. 2. Abnormal right ventricular function on echocardiography or computed tomography pulmonary angiography, defined as right ventricular/left ventricular ratio ≥1.0, and elevated cardiac troponin above the local upper reference limit, and acute respiratory failure not primarily caused by underlying lung disease, defined as requiring facemask oxygen supplementation ≥12 L/min, high-flow nasal oxygen, or non-invasive ventilation with FiO2 ≥60% to reach oxygen saturation ≥94%. 4. Female participants of childbearing potential must have a negative urine or serum pregnancy test. Exclusion Criteria: 1. Catastrophic pulmonary embolism, defined as ongoing cardiac arrest and/or need for extracorporeal cardiopulmonary resuscitation and/or immediate VA-ECMO as judged by the treating physicians. 2. Known hypersensitivity to alteplase or any of its excipients. 3. Contraindication to systemic thrombolysis with one or more of the following: * History of hemorrhagic stroke; * Ischemic stroke within the previous 6 months; * Central nervous system neoplasm; * Major trauma, major surgery, or major head injury within the previous 3 weeks; * Active life-threatening bleeding, bleeding into a critical organ or area, or known severe bleeding diathesis; * Chronic use of full-dose oral or parenteral anticoagulation before presentation. 4. The participant has already received reperfusion treatment for the index pulmonary embolism before randomization, including systemic thrombolysis, surgical embolectomy, or catheter-directed intervention. 5. Pregnancy. 6. Current participation in another study that would interfere with participation in this trial. 7. Any other condition that would put the participant at unacceptable risk from the trial interventions as judged by the treating clinician. 8. In countries where required by national regulations: lack of affiliation to a social security system or equivalent health insurance coverage.