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

Pulmonary Embolism Clinical Trial

— RESUPEC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00968929
• Other study ID #: 2006BAI01A06
• Status: Completed
• Phase: Phase 4
• First received: August 28, 2009
• Last updated: August 31, 2009
• Start date: June 2006
• Est. completion date: May 2009

Study information

• Verified date: August 2009
• Source: Beijing Chao Yang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism
• Pulmonary Thromboembolism
• Thromboembolism

Intervention

Drug:
• Recombinant Streptokinase
Recombinant streptokinase: 1.5 million IU continuously intravenous infusion for 2 hours
• Urokinase
Urokinase: 20,000 IU/kg continuously intravenous infusion for 2 hours

Locations

Country	Name	City	State
China	Beijing Institute of Respiratory Medicine, Beijing Chao-Yang hospital	Beijing	Beijing
China	Guangdong Institute of Respiratory Disease, Guangzhou Medical University,	Guangzhou	Guangdong
China	The Affiliated Hospital of Medical College Qingdao University	Qingdao	Shandong
China	The General Hospital of Shenyang Military Command	Shenyang	Liaoning
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	The First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Affiliated Hospital of Ningxia Medical University	Yinchuan	Ningxia

Sponsors (8)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital	General Hospital of Shenyang Military Region, Guangdong Institute of Respiratory Disease, Ningxia Medical University, Qingdao University, Shenzhen People's Hospital, The First Affiliated Hospital of Shanxi Medical University, Tianjin Medical University General Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Yang Wang, Chen Wang, Yuanhua Yang, Baosen Pang. Effect of recombinant single-chain urokinase-type plasminogen activator on experimental pulmonary embolism. Clin Appl Thromb Hemost. 2010 Oct;16(5):537-42. doi: 10.1177/1076029609343003. Epub 2009 Oct 14. — View Citation

Zhu L, Wang C, Yang Y, Wu Y, Zhai Z, Dai H, Pang B, Tong Z. Value of transthoracic echocardiography in therapy regimens evaluation in pulmonary embolism. J Thromb Thrombolysis. 2008 Dec;26(3):251-6. Epub 2007 Aug 21. — View Citation

Zhu L, Yang Y, Wu Y, Zhai Z, Wang C. Value of right ventricular dysfunction for prognosis in pulmonary embolism. Int J Cardiol. 2008 Jun 23;127(1):40-5. Epub 2007 Aug 22. — View Citation

Zhu L, Yang YH, Wu YF, Zhai ZG, Wang C; National Project of the Diagnosis and Treatment Strategies for Pulmonary Thromboembolism investigators. Value of transthoracic echocardiography combined with cardiac troponin I in risk stratification in acute pulmonary thromboembolism. Chin Med J (Engl). 2007 Jan 5;120(1):17-21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The improvement of the right ventricular function on echocardiogram		within the 1st, 14 days and 3 months	No
Primary	Quantitative computed tomographic pulmonary angiography (CTPA) score		1st, 14 days and 3 months	No
Primary	The relief of symptoms		2-4h, 1st, 4th , 7th, 10th, 14 days day and 3 months	No
Secondary	Major or minor bleeding		14 days and 3 months	Yes
Secondary	Pulmonary embolism recurrence		14 days and 3 months	Yes
Secondary	Death		14 days and 3 months	Yes