Injection of Recombinant Human Tissue-type Plasminogen Activator Derivative for Acute Pulmonary Embolism(rPA)

Inclusion Criteria:

• Patients with high-risk acute pulmonary embolism: the main manifestations are shockand hypotension.Systemic systolic blood pressure <90 millimetre of mercury (mmHg) (1mmHg=0.133kPa), or a decrease from the base value ≥40 millimetre of mercury for morethan 15min.

• Patients with moderate to high-risk acute pulmonary embolism who have worsenedanticoagulant therapy require thrombolytic therapy:

(Patients with moderate to high-risk acute pulmonary embolism: Right ventriculardysfunction (RVD) and elevated cardiac biomarkers coexist.)

1. RVD diagnostic criteria: imaging evidence including echocardiography or CT:1)Ultrasound examination is consistent with the following performance: 1. rightventricular dilatation (right ventricular end-diastolic diameter / left ventricularend-diastolic diameter > 1.0 or 0.9); 2. right ventricular free wall movementamplitude decreased; 3. tricuspid regurgitation speed increased; 4. tricuspid annulussystolic displacement decreased (<17mm); 2) Computed Tomographic Pulmonary Angiographyexamination meets the following conditions: right ventricular dilatation (rightventricular end-diastolic diameter / left ventricular end-diastolic diameter > 1.0 or 0.9) found at the four-chamber heart level;

2. Cardiac biological markers including N terminal pro B type natriuretic peptide (NT-proBNP/BNP) and troponin elevation; Diagnostic criteria for worsening after anticoagulant therapy in patients with moderate tohigh risk acute pulmonary embolism: Hemodynamic deterioration (defined as meeting at least one of the following conditions: 1.requires cardiopulmonary resuscitation; 2. systemic systolic blood pressure <90 mmHg (1mmHg = 0.133 kPa), or a decrease in basal value ≥ 40 mmHg for more than 15 min, or withterminal Low organ perfusion (limb cold or urine volume <30 ml/hr, or mental confusion); 3.need to infuse a booster drug (except dopamine <5 μg/kg/min) to maintain adequate tissueperfusion and systolic blood pressure > 90 mmHg ;

• The time from onset to the time of thrombolysis is ≤ 14 days;

• Male patients must agree to take effective contraceptive measures during treatment andat least 28 days after the end of the trial, and do not donate sperm during thisperiod; women of childbearing age must be negative within the first 72 hours ofrandomization, and agree to adopt effective contraceptive measures during treatmentand at least 28 days afterwards the last treatment.

• Voluntary signing of written informed consent form.

Exclusion Criteria:

• a history of hemorrhagic stroke or unexplained stroke;

• Ischemic stroke or transient ischemic attack within 3 months;

• Central nervous system damage or tumor;

• Surgery and trauma of the brain or spine within 2 months;

• Active internal bleeding within 1 month (such as gastrointestinal bleeding,hemoptysis, blood in the stool, etc.);

• High risk of bleeding: evidence or history of bleeding disorders, bleeding tendency,bleeding constitution or coagulopathy;

• oral anticoagulant (can be randomized after a certain period of time, such as oralrivaroxaban can be randomized after 1 day of elution, oral warfarin can be performedat International Normalized Ratio <2.0 random);

• 1 week after pregnancy or delivery;

• vascular puncture of the site that cannot be oppressed;

• Cardiopulmonary resuscitation within 10 days;

• Hypertension that is difficult to control (systolic blood pressure > 180 mmHg and / ordiastolic blood pressure ≥ 110 mmHg);

• Liver function is grade C of Child-Pugh ;

• Infective endocarditis;

• History of aneurysms or arteriovenous malformations, or suspected aortic dissection;

• Cardiac thrombosis;

• Diabetes with hemorrhagic retinopathy or other hemorrhagic eye diseases;

• Laboratory inspection:Platelets (PLT) <90×109/L;Alanine aminotransferase (ALT) > 2.5 ×ULN, aspartate aminotransferase (AST) > 2.5 ×Upper Limit of Normal (ULN);Endogenouscreatinine clearance (Ccr) ≤ 50ml/min (calculated according to the Cockcroft-Gaultformula);Alkaline phosphatase (ALP) > 2.0 × ULN;

• Severe cardiac insufficiency occurred in the past 6 months, New York Heart AssociationHeart Function Rating (NYHA classification) ≥ III;

• Participate in other clinical trials within 1 month prior to enrollment;

• Known or suspected hypersensitivity to plasminogen activator, or allergic to contrastagents, or drugs administered during the trial;

• People with mental disorders;

• Accompanied by other serious diseases that may prevent them from entering or affectingtheir survival, such as cancer or AIDS;

• Any disease or condition that is not suitable for intravenous thrombolysis;

• Other diseases or conditions that the investigator believes are not suitable for thetrial.