Low Dosage of rt-PA in the Treatment of Pulmonary Thromboembolism in China

Pulmonary Embolism Clinical Trial

Official title:

Efficacy and Safety Evaluation of Low Dosage of Recombinant Tissue Plasminogen Activator (rt-PA) in the Treatment of Pulmonary Thromboembolism: A Multi-Center, Randomized Controlled Trial in China

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00781378
• Other study ID #: 2001BA703B13
• Secondary ID: 2004BA703B07
• Status: Completed
• Phase: Phase 4
• First received: October 21, 2008
• Last updated: October 28, 2008
• Start date: June 2002
• Est. completion date: February 2006

Study information

• Verified date: October 2008
• Source: Beijing Chao Yang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Recombinant tissue plasminogen activator (rt-PA) is currently the most commonly used thrombolytic drug in patients with pulmonary thromboembolism (PTE). Optimal dosing with maximal benefits and minimal risks is of great importance. Considering the lower body weight in general Chinese population, we compared the efficacy and safety of lower dose rt-PA 50mg/2h regimen with the FDA-approved rt-PA 100mg/2h regimen in selected PTE patients.

Description:

Pulmonary thromboembolism (PTE) is a severe and common clinical problem with substantial morbidity and mortality both in US and in Europe. Used to be considered as a rare disease in China, PTE has been increasingly diagnosed in recent years due to the increased awareness and the improvement of imaging techniques. PTE is life threatening without proper intervention at the early onset. Effective treatment can decrease the mortality and the complication of chronic thromboembolic pulmonary hypertension (CTEPH).

Recombinant tissue-type plasminogen activator (rt-PA) is currently the most commonly used drug for PTE thrombolysis. Like most thrombolytic medications, rt-PA carries a risk of significant bleeding, which is dose dependent. Thus, optimal dosing that can maximize benefits and minimize risks is of great importance. There is substantial controversy and debate regarding the optimal rt-PA dosage for thrombolytic therapy and whether the same dose should be used in all patients. Low dose of intravenous rt-PA for thrombolysis after acute myocardial infarction (AMI) had been suggested by previous studies. Experimental and clinical studies have indicated that a lower dose of rt-PA bolus may be potentially safer, and yet equally effective then the 2-h 100 mg rt-PA continuous infusion for PTE.

Considering lower body weight in Chinese population, a lower dose of 50mg rt-PA/2h may exhibit similar efficacy and safety as 100mg/2-h rt-PA for treating acute PTE in this population. We, therefore, compared these two regimens in a multi-center, randomized, controlled trial. The efficacy was assessed by the improvement of the right ventricular function on echocardiograms, perfusion defect score of lung V/Q scans or quantitative computed tomographic (CT) evaluation, safety was evaluated by incidence of major or minor bleeding, death rate, and PTE recurrence on 24h,14d after treatment.

110 patients will be randomized in the study. The patients included in the study will be randomized, in a double blind fashion, to receive rt-PA 100mg 2h (55 patients) or rt-PA50mg 2h(55 patients).Study treatment should be administered within 72 hours from echocardiography. Echocardiography will be repeated at 24 hours and 14 days from rt-PA injection. A Follow-up visit at 14 days from randomization will include: clinical history, physical examination and ECG and an echocardiographic examination CTPA and V/Q scan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• 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:

• age between 18 and 75

• symptomatic PE confirmed by: a high probability ventilation-perfusion lung scanning (V/Q scan) or the presence of intraluminal filling defect on spiral computed tomographic pulmonary angiography (CTPA)

• PTE patients with haemodynamic instability, or cardiogenic shock

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

• written informed consent

Exclusion Criteria:

• active bleeding or spontaneous intracranial hemorrhage

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

• cerebral arterial thrombosis within 2 months

• gastro-intestinal bleeding within 10 days

• major trauma within the past 15 days

• neurosurgery or ophthalmologic operation with 30 days

• 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 with 2 weeks

• infectious pericarditis or endocarditis

• severe hepatic and kidney dysfunction

• hemorrhagic retinopathy due to diabetes

• a known bleeding disorder

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Embolism
• Thromboembolism

Intervention

Drug:
• rt-PA
rt-PA 100 mg continuous intravenous infusion for 2 hours
• rt-PA
rt-PA 50 mg continuous intravenous infusion for 2 hours

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital, Capital University of Medical Sciences	Beijing	Beijing
China	Beijing University People's Hospital	Beijing	Beijing
China	Peking Union Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	The Omni-hospital of Air-force	Beijing	Beijing
China	Guangzhou Institute of Respiratory Disease	Guangdong	Guangzhou
China	Zhejiang Shaoyifu Hospital	Hangzhou	Zhenjiang
China	Qilu Hospital of Shandong University	Jinan	Shangdong
China	The First Affiliated Hospital of Jining Medical College	Jinan	Shangdong
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The First Affiliated Hospital of Qingdao University CHENG Zhao-zhong	Qingdao	Shangdong
China	Shanghai Hospital of Lung Disease	Shanghai	Shanghai
China	Shanghai Ruijin Hospital HUANG Shao-guang	Shanghai	Shanghai
China	Shenyang Military Hospital	Shenyang	Liaoning
China	The Affiliated Hospital of Shenyang Medical University	Shenyang	Liaoning
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	The Second Affiliated Hospital of Hebei University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Shanxi University	Tai-yuan	Shanxi
China	The Second Affiliated Hospital of Shanxi University	Tai-yuan	Shanxi
China	Tianjin Hospital of Medical Sciences	Tianjin	Tianjin
China	The Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Shangdong Yantaishan Hospital	Yantai	Shandong
China	The Affiliated Hospital of Ningxia Medical University	Yinchuang	Ningxia
China	The First Affiliated Hospital of Zhengzhou University:	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The improvement of the right hart function on echocardiograms		within the 1st 14 days	No
Primary	Perfusion defect score of lung V/Q scans		within the 1st 14 days	No
Primary	Quantitative computed tomographic pulmonary angiography (CTPA) score on 2d, 14d after treatment.		within the 1st 14 days	No
Secondary	Major or minor bleeding		within 1st 14 days	Yes
Secondary	PE recurrence		within the 1st 14 days	Yes
Secondary	Death		within the 1st 14 days	Yes