A Trial in Recombinant Human Prourokinase to Treat Acute Pulmonary Embolism

Study Overview
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Brief Summary
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This trial is being conducted to assess the efficacy and safety of recombinant Human Prourokinase in the acute pulmonary embolism.

Official Title
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A Phase IIa Trial to Assess the Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Pulmonary Embolism

Conditions
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Acute Pulmonary Embolism

Intervention / Treatment
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* Drug: Recombinant Human Prourokinase
* Drug: Alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-75 years（Include the critical value）AND High-risk PE or medium high-risk PE AND PE symptom duration ≤14 days AND PLT≥100×10^9/L，ALT and AST≤2.5ULN，TBIL<ULN，Cr within the normal range AND Informed consent can be obtained from subject or Legally Authorized Representative Exclusion Criteria: Hemorrhagic or unexplained stroke history Ischemic stroke or transient ischemic attack (TIA) within 6 months The existence of the central nervous system injury or tumor Severe trauma，major surgery or head injury within 3 weeks Active bleeding within 1 month Clinician deems high-risk for bleeding Using anticoagulants (after a washout period can be randomized) Pregnancy or delivery within 1 week Vascular puncture which can not be oppressed Cardiopulmonary resuscitation within 10 days Systolic blood pressure above 180 mmHg or diastolic blood pressure above 100mmHg Severe liver dysfunction Infective endocarditis Arterial aneurysm or arteriovenous malformation or suspected aortic dissection left atrial thrombus Neurosurgery or eye surgery within 1 month Hemorrhagic diabetic retinopathy Serious cardiac insufficiency ventricular arrhythmias Known allergic to prourokinase，urokinase，recombinant tissue-type plasminogen activator，contrast agent or any drug in the trial Do not allow for 30 days' study Any disease or condition is not suitable for intravenous thrombolysis Lactating women or plan to pregnant women during the trial，or don't want to during the study period using effective contraception or abstinence of male and female patients with possibility of fertility Clinician thinks patient doesn't fit to participate in the test of other diseases or conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Experimental Group<br>Recombinant Human Prourokinase:40mg | Drug: Recombinant Human Prourokinase<br>* The drug is used for intravenous thrombolysis therapy<br>* Other names: rhPro-UK;|
| Experimental: High Dose Experimental Group<br>Recombinant Human Prourokinase:50mg | Drug: Recombinant Human Prourokinase<br>* The drug is used for intravenous thrombolysis therapy<br>* Other names: rhPro-UK;|
| Active Comparator: Active Comparator Controlled Group<br>Alteplase:100mg if weight>=65kg, 1.5mg/kg if weight<65kg | Drug: Alteplase<br>* The drug is used for intravenous thrombolysis therapy<br>* Other names: rtPA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qanadli CT Score | Change of Qanadli Score from baseline by CTPA 48hours after treatment | 0 and 48hours after treatment | 
| Average pulmonary artery pressure | Changes of average pulmonary artery pressure from baseline 24hours，48hours，7days and 30days after treatment | 0,24hours，48hours，7days and 30days after treatment | 
| Three tricuspid regurgitation velocity | Changes of Three tricuspid regurgitation velocity from baseline 24hours，48hours，7days and 30days after treatment | 0,24hours，48hours，7days and 30days after treatment | 
| RV to LV Diameter Ratio(Ultrasonic echocardiography) | Changes of RV to LV Diameter Ratio from baseline 24hours，48hours，7days and 30days after treatment | 0,24hours，48hours，7days and 30days after treatment | 
| RV to LV Diameter Ratio(CTPA) | Changes of RV to LV Diameter Ratio from baseline 24hours，48hours，7days and 30days after treatment | 0,24hours，48hours，7days and 30days after treatment | 
| Pulmonary systolic pressure | Changes of pulmonary systolic pressure from baseline 24hours，48hours，7days and 30days after treatment | 0,24hours，48hours，7days and 30days after treatment | 
| NT-proBNP | Changes of NT-proBNP from baseline 48hours and 30days after treatment | 0，48hours and 30days after treatment | 
| Major bleeding | The frequency of major bleeding | From baseline to 30 days | 
| bleeding | The frequency of bleeding | From baseline to 30 days | 
| Incidence of death from all causes | Incidence of death from all causes | From baseline to 7 days | 
| Incidence of recurrent pulmonary embolism | Incidence of recurrent pulmonary embolism | From baseline to 7 days | 
| Incidence of death from all causes | Incidence of death from all causes | From baseline to 30 days | 
| Incidence of hemodynamic deterioration | Incidence of hemodynamic deterioration | From baseline to 7 days |