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

This study has been completed.
Sponsor:
Collaborators:
Qingdao University
Tianjin Medical University General Hospital
General Hospital of Shenyang Military Region
Guangdong Institute of Respiratory Disease
The First Affiliated Hospital of Shanxi Medical University
Shenzhen People's Hospital
Ningxia Medical University
Information provided by:
Beijing Chao Yang Hospital
ClinicalTrials.gov Identifier:
NCT00968929
First received: August 28, 2009
Last updated: August 31, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Pulmonary Embolism
Pulmonary Thromboembolism
Drug: Recombinant Streptokinase
Drug: Urokinase
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Beijing Chao Yang Hospital:

Primary Outcome Measures:
  • The improvement of the right ventricular function on echocardiogram [ Time Frame: within the 1st, 14 days and 3 months ] [ Designated as safety issue: No ]
  • Quantitative computed tomographic pulmonary angiography (CTPA) score [ Time Frame: 1st, 14 days and 3 months ] [ Designated as safety issue: No ]
  • The relief of symptoms [ Time Frame: 2-4h, 1st, 4th , 7th, 10th, 14 days day and 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Major or minor bleeding [ Time Frame: 14 days and 3 months ] [ Designated as safety issue: Yes ]
  • Pulmonary embolism recurrence [ Time Frame: 14 days and 3 months ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 14 days and 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 83
Study Start Date: June 2006
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: r-SK group
Recombinant streptokinase: 1.5 million IU continuously intravenous infusion for 2 hours
Drug: Recombinant Streptokinase
Recombinant streptokinase: 1.5 million IU continuously intravenous infusion for 2 hours
Active Comparator: UK group
Urokinase: 20,000 IU/kg continuously intravenous infusion for 2 hours
Drug: Urokinase
Urokinase: 20,000 IU/kg continuously intravenous infusion for 2 hours

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00968929

Locations
China, Beijing
Beijing Institute of Respiratory Medicine, Beijing Chao-Yang hospital
Beijing, Beijing, China, 100020
China, Guangdong
Guangdong Institute of Respiratory Disease, Guangzhou Medical University,
Guangzhou, Guangdong, China, 510120
Shenzhen People's Hospital
Shenzhen, Guangdong, China, 518020
China, Liaoning
The General Hospital of Shenyang Military Command
Shenyang, Liaoning, China, 110016
China, Ningxia
Affiliated Hospital of Ningxia Medical University
Yinchuan, Ningxia, China, 750004
China, Shandong
The Affiliated Hospital of Medical College Qingdao University
Qingdao, Shandong, China, 266003
China, Shanxi
The First Affiliated Hospital of Shanxi Medical University
Taiyuan, Shanxi, China, 030001
China, Tianjin
Tianjin Medical University General Hospital
Tianjin, Tianjin, China, 300052
Sponsors and Collaborators
Beijing Chao Yang Hospital
Qingdao University
Tianjin Medical University General Hospital
General Hospital of Shenyang Military Region
Guangdong Institute of Respiratory Disease
The First Affiliated Hospital of Shanxi Medical University
Shenzhen People's Hospital
Ningxia Medical University
Investigators
Principal Investigator: Chen WANG, Prof Beijing Institute of Respiratory Medicine, Beijing-Chao Yang Hospital
  More Information

Publications:
Responsible Party: Chen WANG, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital
ClinicalTrials.gov Identifier: NCT00968929     History of Changes
Other Study ID Numbers: 2006BAI01A06
Study First Received: August 28, 2009
Last Updated: August 31, 2009
Health Authority: China: Food and Drug Administration

Keywords provided by Beijing Chao Yang Hospital:
pulmonary embolism
thrombolysis
massive
submassive
recombinant streptokinase
urokinase

Additional relevant MeSH terms:
Embolism
Pulmonary Embolism
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Thrombosis
Streptokinase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on August 28, 2014