Clinical trial NCT00968929: Recombinant Streptokinase Versus Urokinase in Pulmonary Embolism in China (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Embolism
Pulmonary Thromboembolism
Keywords: pulmonary embolism
thrombolysis
massive
submassive
recombinant streptokinase
urokinase
Lead sponsor: Beijing Chao Yang Hospital
Sponsor class: OTHER
Collaborators: name: Qingdao University
name: Tianjin Medical University General Hospital
name: General Hospital of Shenyang Military Region
name: Guangdong Institute of Respiratory Disease
name: The First Affiliated Hospital of Shanxi Medical University
name: Shenzhen People's Hospital
name: Ningxia Medical University
First posted: 2009-08-31
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: The improvement of the right ventricular function on echocardiogram
timeFrame: within the 1st, 14 days and 3 months
measure: Quantitative computed tomographic pulmonary angiography (CTPA) score
timeFrame: 1st, 14 days and 3 months
measure: The relief of symptoms
timeFrame: 2-4h, 1st, 4th , 7th, 10th, 14 days day and 3 months
Secondary outcomes:
measure: Major or minor bleeding
timeFrame: 14 days and 3 months
measure: Pulmonary embolism recurrence
timeFrame: 14 days and 3 months
measure: Death
timeFrame: 14 days and 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Institute of Respiratory Medicine, Beijing Chao-Yang hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Institute of Respiratory Disease, Guangzhou Medical University,
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military Command
state: Liaoning
city: Yinchuan
country: China
facility: Affiliated Hospital of Ningxia Medical University
state: Ningxia
city: Qingdao
country: China
facility: The Affiliated Hospital of Medical College Qingdao University
state: Shandong
city: Taiyuan
country: China
facility: The First Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Beijing Institute of Respiratory Medicine, Beijing-Chao Yang Hospital
name: Chen WANG, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/j.ijcard.2007.06.093. Epub 2007 Aug 22.
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.
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. doi: 10.1007/s11239-007-0087-8. Epub 2007 Aug 21.
citation: 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.