12-h and 2-h Urokinase Regimes of Pulmonary Thromboembolism in China

Pulmonary Embolism Clinical Trial

— UKPTEC  

Official title:

Efficacy and Safety Evaluation of 12-h and 2-h Urokinase Regimes in the Treatment of Pulmonary Thromboembolism: A Multi-Center, Randomized Controlled Trial in China

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00799968
• Other study ID #: 2004BA703B07-UK
• Status: Completed
• Phase: Phase 4
• First received: November 28, 2008
• Last updated: November 28, 2008
• Start date: June 2002
• Est. completion date: February 2006

Study information

• Verified date: November 2008
• Source: Beijing Chao Yang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Comparative trials of urokinase (UK) for 12 hours（UK-12h）or 24 hours (UK-24h) have produced similar results in acute pulmonary thromboembolism (PTE) thrombolysis. It is unclear whether the infusion time can be reduced further. The aim of this study was to investigate the efficacy and safety of weight adjusted dosage of UK-2h (20 000 IU/Kg) regime with the Uk-12h regime in selected patients with PTE in Chinese population.

Description:

Pulmonary thromboembolism (PTE), a frequent life-threatening complication of deep vein thrombosis (DVT), is often underestimated and under diagnosed . Effective early treatment will decrease the mortality, reverse right heart dysfunction and reduce risk of chronic thromboembolic pulmonary hypertension (CTEPH) or post-thrombotic syndrome (PTS). Thrombolysis has proved to be the most rapid and effective therapy to reduce the obstruction of pulmonary circulation and normalize hemodynamic parameters. The ultimate goals of thombolytic 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 (either UK or rt-PA) is mostly based on personal or regional preferences. A loading dose of UK 4400 IU/kg followed by 2200 IU/kg/hour for 12 hours (UK-12h), or rt-PA 100 mg infusion over 2 hours are recommended for acute PTE treatment. However, increasing evidence suggest that UK infusion can be more concentrated and time can be further reduced. 100 mg/2 h of rt-PA and a novel dosing regimen of UK(3 million U/2 h) had been compared. The results indicated that a 2-h regimen of rt-PA and 2h UK exhibited similar efficacy and safety for treatment of acute PTE. UK-2h(20 000U/Kg) regimen combined with low molecular weight heparin (LMWH) had been used in Chinese population.No severe bleeding and allergic reaction occurred in the thrombolytic group. This dosage is much lower than that used by Goldhaber et al, but the efficacy was prominent. Until now,no study have been reported to compared UK-2h(20 000U/Kg) regimen with other UK regimens(such as UK-12h).

A relative lower dosage of UK 2-h regimen with body weight adjusted may be an alternative choice for treating PTE patients in Chinese population.Considering lower cost and convenience of this regimen, the efficacy and safety between UK-2h regimen(20 000U/Kg) and ACCP-approved UK-12h regimen for treating acute PTE will be compared.The study is conducted on patients with massive PTE with shock or hypotension and/or if without shock or hypotension but with right ventricular dysfunction. The clinical efficacy, emboli dissolving efficacy and safety will be evaluated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• PTE confirmed either by a high probability ventilation-perfusion lung scanning (V/Q scan) or by CTPA.

• massive PTE patients with haemodynamic instability and/or cardiogenic shock

• Anatomic obstruction more than 2 lobes on CTPA and/or defect more than 7 segments on V/Q scan with evidence of right ventricular dysfunction (RVD) and pulmonary hypertension on echocardiography

• Symptoms within 15 days

• Written informed consent was obtained from all the patients before randomization

Exclusion Criteria:

• Received parenteral heparin for more than 72 hours

• Known allergic to urokinase

• Thrombolytic contraindications such as:

1. active bleeding or spontaneous intracranial hemorrhage;

2. major surgery, organ biopsy or recent puncture of a non-compressible vessel less than 10 days;

3. cerebral arterial thrombosis within 2 months;

4. gastro-intestinal bleeding within 10 days;

5. major trauma within the past 15 days;

6. neurosurgery or ophthalmologic operation with 30 days;

7. uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg);

8. recent external cardiac resuscitation manoeuvres;

9. platelet count < 100 000/mm3 at admission;

10. pregnancy, puerperium or lactation with 2 weeks;

11. infectious pericarditis or endocarditis;

12. severe hepatic and kidney dysfunction;

13. hemorrhagic retinopathy due to diabetes;

14. a known bleeding disorder.

Study Design

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

Related Conditions & MeSH terms

• Pulmonary Embolism
• Thromboembolism

Intervention

Drug:
• Urokinase
UK,bolus 4 400 U/kg followed by intravenous 2 200 U/kg•h for 12 hours
• Urokinase
UK,20 000U/kg continuously intravenous infusion for 2 hours

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital, Capital University of Medical Sciences	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Fu Xing Hospital, Capital Medical University	Beijing	Beijing
China	Beijing General Hospital of the Air-force PLA	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Beijing Naval General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The Fifth People's Hospital of Datong in ShanxiWANG;	Datong	Shanxi
China	Guangzhou Institute of Respiratory Disease,Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital Sun Yat-Sen University	Guangzhou	Guandong
China	Sir Run Run Shaw Hospital, Affiliated with Zhejiang University	Hangzhou	Zhejiang
China	Qilu Hospital Affiliated to Shandong University	Jinan	Shandong
China	The First Affiliated Hospital of Jining Medical College	Jinan	Shangdong
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The Affiliated Hospital of Medical College Qingdao	Qingdao	Shandong
China	The First Affiliated Hospital of Qingdao University CHENG Zhao-zhong	Qingdao	Shangdong
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	The General Hospital of Shenyang Military Command	Shenyang	Liaoning
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	The Second Affiliated Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	The Second Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tangshan Worker's Hospital, Hebei Medical University	Tangshan	Hebei
China	The Affiliated Hospital of Hubei Coal University	Tangshan	Hebei
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tianjin Thoracic Hospital	Tianjin	Tianjin
China	Xinjiang People's Hospital	Urumqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Wuhan Union Hospital	Wuhan	Hubei
China	Shangdong Yantaishan Hospital	Yantai	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital

Country where clinical trial is conducted

China, 

References & Publications (14)

Liu CP, Zhang YJ, Lu WX, Ji YQ, Zhang WH, Wang C. [The change of pulmonary surfactant associated protein A in acute pulmonary embolism]. Zhonghua Jie He He Hu Xi Za Zhi. 2005 Sep;28(9):600-3. Chinese. — View Citation

Liu Y, Wang C, Yang Y, Hou X, Wang J. Pro-urokinase up-regulates the expression of urokinase-type plasminogen activator (u-PA) in human pulmonary arterial endothelial cells. Thromb Res. 2008;121(4):485-91. Epub 2007 Jul 20. — View Citation

Pang BS, Wang C, Lu Y, Yang YH, Xing GH, Mao YL, Huang XX, Zhai ZG. [Changes of blood coagulative and fibrinolytic system and function of pulmonary vascular endothelium after therapy in patients with acute pulmonary thromboembolism]. Zhonghua Yi Xue Za Zhi. 2007 Nov 20;87(43):3074-8. Chinese. — View Citation

Pang BS, Wang C, Luo Q, Zhang LM, Zhu M, Mao YL, Huang XX, Guo WJ. [Study of the function of coagulation, fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Jun;27(6):381-4. Chinese. — View Citation

Qin ZQ, Wang C. [Comparison of thrombolysis and anticoagulation in pulmonary thromboembolism: a meta-analysis]. Zhonghua Jie He He Hu Xi Za Zhi. 2003 Dec;26(12):772-5. Chinese. — View Citation

Ren H, Su PX, Zhang CJ, Gu S, Ma GT, Zhang H, Wang C. [Surgical treatment of chronic pulmonary thromboembolism]. Zhonghua Wai Ke Za Zhi. 2005 Mar 15;43(6):345-7. Chinese. — View Citation

Wang C, Cheng XS, Zhong NS. [Promoting the clinical and research work on pulmonary thromboembolism in China]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Nov;27(11):721-2. Chinese. — View Citation

Wang F, Wang C, Wang T, Pang BS, Wu YB, Yang YH, Li C, Zhang HY, Weng XZ. [A canine model of acute pulmonary thromboembolism induced by autologous radioactive blood clots]. Zhonghua Jie He He Hu Xi Za Zhi. 2003 Aug;26(8):470-3. Chinese. — View Citation

Wang F, Wang C, Wang T, Pang BS, Wu YB, Yang YH, Li C, Zhang HY, Weng XZ. [Experimental study of the thrombolytic effects in a canine model of pulmonary thromboembolism induced by autologous radioactive blood clots]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Feb;27(2):93-6. Chinese. — View Citation

Zai ZG, Wang C. [Advances in the study of pulmonary thromboembolism]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Jan;27(1):14-8. Review. Chinese. — View Citation

Zhai ZG, Wang C, Yang YH, Pang BS, Xiao B, Liu YM, Mao YL, Weng XZ. [Relationship between polymorphisms of plasminogen activator inhibitor-1 promoter gene and pulmonary thromboembolism in Chinese Han population]. Zhonghua Yi Xue Za Zhi. 2006 May 23;86(19):1313-7. Chinese. — 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

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The improvement of the right ventricular function , perfusion defect score on lung V/Q scans or quantitative computed tomographic pulmonary angiography (CTPA) score.		14d	No
Secondary	The incidence of major or minor bleeding, death rate, and PTE recurrence at 14d after treatment.		14d	Yes