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

Phase 4

Completed

• Conditions: Pulmonary Embolism; Pulmonary Thromboembolism
• Interventions: Drug: Recombinant Streptokinase; Drug: Urokinase

• Registration Number: NCT00968929
• Lead Sponsor: Beijing Chao Yang Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2006-06
• Primary Completion: 2009-05
• Study Completion: 2009-05
• Status Verified: 2009-08
• Study First Submitted: 2009-08-28
• Study First Submitted QC: 2009-08-28
• Study First Posted: 2009-08-31
• Last Update Submitted: 2009-08-31
• Last Update Posted: 2009-09-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
r-SK group	Recombinant Streptokinase	Recombinant streptokinase: 1.5 million IU continuously intravenous infusion for 2 hours
UK group	Urokinase	Urokinase: 20,000 IU/kg continuously intravenous infusion for 2 hours

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Pulmonary embolism recurrence	14 days and 3 months
Death	14 days and 3 months
Major or minor bleeding	14 days and 3 months

Trial Locations

Locations (8)

The General Hospital of Shenyang Military Command; 🇨🇳 Shenyang, Liaoning, China

Shenzhen People's Hospital; 🇨🇳 Shenzhen, Guangdong, China

Guangdong Institute of Respiratory Disease, Guangzhou Medical University,; 🇨🇳 Guangzhou, Guangdong, China

Beijing Institute of Respiratory Medicine, Beijing Chao-Yang hospital; 🇨🇳 Beijing, Beijing, China

Affiliated Hospital of Ningxia Medical University; 🇨🇳 Yinchuan, Ningxia, China

The Affiliated Hospital of Medical College Qingdao University; 🇨🇳 Qingdao, Shandong, China

The First Affiliated Hospital of Shanxi Medical University; 🇨🇳 Taiyuan, Shanxi, China

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, Tianjin, China