Clinical trial NCT00799968: 12-h and 2-h Urokinase Regimes of Pulmonary Thromboembolism in China
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Embolism
Thromboembolism
Keywords: Thrombolytic therapy
Urokinase
Efficacy
Safety
Lead sponsor: Beijing Chao Yang Hospital
Sponsor class: OTHER
First posted: 2008-12-01
Enrollment: 129
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: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The improvement of the right ventricular function , perfusion defect score on lung V/Q scans or quantitative computed tomographic pulmonary angiography (CTPA) score.
timeFrame: 14d
Secondary outcomes:
measure: The incidence of major or minor bleeding, death rate, and PTE recurrence at 14d after treatment.
timeFrame: 14d
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chaoyang Hospital, Capital University of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing General Hospital of the Air-force PLA
state: Beijing
city: Beijing
country: China
facility: Beijing Fu Xing Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Naval General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital Sun Yat-Sen University
state: Guandong
city: Guangzhou
country: China
facility: Guangzhou Institute of Respiratory Disease，Guangzhou Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: The Second Affiliated Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Tangshan Worker's Hospital, Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: The Affiliated Hospital of Hubei Coal University
state: Hebei
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military Command
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital Affiliated to Shandong University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Medical College Qingdao
state: Shandong
city: Yantai
country: China
facility: Shangdong Yantaishan Hospital
state: Shandong
city: Jinan
country: China
facility: The First Affiliated Hospital of Jining Medical College
state: Shangdong
city: Qingdao
country: China
facility: The First Affiliated Hospital of Qingdao University CHENG Zhao-zhong
state: Shangdong
city: Datong
country: China
facility: The Fifth People's Hospital of Datong in ShanxiWANG;
state: Shanxi
city: Taiyuan
country: China
facility: The First Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: The Second Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Thoracic Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Urumqi
country: China
facility: Xinjiang People's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Affiliated with Zhejiang University
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical College
state: Zhejiang
Study officials:
affiliation: Beijing Institute of Respiratory Medicine,Beijing Chao Yang Hospital
name: Chen WANG, Prof
role: PRINCIPAL_INVESTIGATOR
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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. No abstract available. Chinese.
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.
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.
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. No abstract available. Chinese.
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.
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.
citation: Wang C, Zhai Z, Yang Y, Yuan Y, Cheng Z, Liang L, Dai H, Huang K, Lu W, Zhang Z, Cheng X, Shen YH; China Venous Thromboembolism Study Group. Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial. Respir Res. 2009 Dec 29;10(1):128. doi: 10.1186/1465-9921-10-128.