Recombinant Streptokinase Versus Urokinase in Pulmonary Embolism in China (RESUPEC)

Study Overview
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Brief Summary
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Recombinant streptokinase (r-SK) is an effective thrombolytic agent developed with gene engineering. Its characteristics of high output and low production cost make it affordable in treating acute myocardial infarction (AMI) in developing countries. It is unclear whether r-SK can be used in patients with pulmonary embolism (PE). The aim of this study was to investigate the efficacy and safety of 1.5 million IU r-SK by 2 hours infusion and 20,000 IU/kg urokinase (UK) by 2 hours infusion in selected PE patients.

Detailed Description
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Pulmonary embolism (PE) is a common cardiovascular illness. Massive PE is characterized with cardiogenic shock and/or persistent arterial hypotension. Submassive PE patients are defined with right ventricular dysfunction (RVD) identified by echocardiography or CT and the etc. The mortality of massive and submassive PE is higher than low-risk PE. PE has the mortality rate of >15% in the first 3 months after diagnosis. Thrombolytic treatment should be commenced as soon as possible after high-risk PE was diagnosed. Thrombolysis has been proved to be the most rapid and effective therapy to reduce the obstruction of pulmonary circulation and normalize hemodynamic parameters. The ultimate goals of thrombolytic therapy for this disease are to minimize early morbidity and mortality and to prevent recurrence without provoking excessive bleeding. Currently, the choice of thrombolytic agents and regimens (SK, UK or rt-PA) is mostly based on personal or regional preferences. A novel dosing regimen of UK (3 million IU/2h, or 4400 IU/kg as a loading dose followed by 4400 IU/kg/h over 12h) and SK (1.5 million IU /2h) have been recommended in ESC guidelines. Considering lower body weight in Chinese population, a relative lower dosage UK-2h (20,000 IU/kg) regimen combined with low molecular weight heparin (LMWH) has been used in Chinese population. Our previous study has revealed that the efficacy and safety of UK-2h (20 000 IU/Kg) were similar with UK-12h (standard regimen) in Chinese patients. Thus the UK-2h (20,000 IU/Kg) became a popular and alternative choice in treating PE in China for its lower cost and convenience. Natural streptokinase (n-SK or SK) is an old thrombolytic agent. However, its immunogenicity lowers its safety and that constitute a concern among doctors. In recent years, as the development of gene engineering, r-SK was produced. R-SK has the advantage of not containing streptolysin and streptodornase unlike streptococci-derived n-SK which might make it safer theoretically. For its low cost, r-SK has been used to treat AMI especially in developing countries. In this study, the efficacy and safety between r-SK (1.5 million IU/2h) and UK-2h (20 000U/Kg) for treating acute PE will be compared. The study is conducted in patients with massive PE and submassive PE. The clinical efficacy, emboli dissolving efficacy and safety will be evaluated.

Official Title
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Efficacy and Safety Evaluation of Recombinant Streptokinase and Urokinase in the Treatment of Pulmonary Embolism: A Multi-Center, Randomized Controlled Trial in China

Conditions
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Pulmonary Embolism, Pulmonary Thromboembolism

Intervention / Treatment
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* Drug: Recombinant Streptokinase
* Drug: Urokinase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic PTE confirmed either by CTPA or by a high probability ventilation-perfusion lung scanning (V/Q scan). Presented with hemodynamic instability (systolic blood pressure <90 mmHg or a fall in systolic blood pressure of more than 40 mmHg for at least 15 min, or cardiogenic shock) or associated with RVD identified by echocardiography or CT. Symptoms deterioration less than 14 days before diagnosis. Exclusion Criteria: Active bleeding or spontaneous intracranial hemorrhage in the preceding 6 months Major surgery, organ biopsy or recent puncture of a non-compressible vessel in the preceding 2 weeks Cerebral arterial thrombosis in the preceding 2 months Gastro-intestinal bleeding in the preceding 10 days Major trauma within the past 15 days Neurosurgery or ophthalmologic operation in the preceding 1 month Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg) Recent external cardiac resuscitation manoeuvres Platelet count < 100,000/mm3 at admission Pregnancy, puerperium or lactation in the preceding 2 weeks Infectious pericarditis or endocarditis Severe hepatic and kidney dysfunction Hemorrhagic retinopathy due to diabetes A known bleeding disorder. Chronic thromboembolic pulmonary hypertension (CTEPH) without new pulmonary thromboembolism (PTE) Received streptokinase in the preceding 6 months Infected by streptococcus in the preceding 1 month.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: r-SK group<br>Recombinant streptokinase: 1.5 million IU continuously intravenous infusion for 2 hours | Drug: Recombinant Streptokinase<br>* Recombinant streptokinase: 1.5 million IU continuously intravenous infusion for 2 hours<br>|
| Active Comparator: UK group<br>Urokinase: 20,000 IU/kg continuously intravenous infusion for 2 hours | Drug: Urokinase<br>* Urokinase: 20,000 IU/kg continuously intravenous infusion for 2 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The improvement of the right ventricular function on echocardiogram |  | within the 1st, 14 days and 3 months | 
| Quantitative computed tomographic pulmonary angiography (CTPA) score |  | 1st, 14 days and 3 months | 
| The relief of symptoms |  | 2-4h, 1st, 4th , 7th, 10th, 14 days day and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major or minor bleeding |  | 14 days and 3 months | 
| Pulmonary embolism recurrence |  | 14 days and 3 months | 
| Death |  | 14 days and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary embolism, thrombolysis, massive, submassive, recombinant streptokinase, urokinase