Low Dosage of rt-PA in the Treatment of Pulmonary Thromboembolism in China
Information source: Beijing Chao Yang Hospital
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pulmonary Embolism; Thromboembolism
Intervention: rt-PA (Drug); rt-PA (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Beijing Chao Yang Hospital Official(s) and/or principal investigator(s): Chen WANG, Prof, Principal Investigator, Affiliation: Beijing Institute of Respiratory Medicine,Beijing Chao-Yang Hospital,Capital Medical University
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: The improvement of the right hart function on echocardiogramsPerfusion defect score of lung V/Q scans Quantitative computed tomographic pulmonary angiography (CTPA) score on 2d, 14d after treatment.
Secondary outcome: Major or minor bleedingPE recurrence Death
Detailed 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing, Beijing 100020, 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
Shenzhen People's Hospital, Shenzhen, Guangdong, China
The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Guangzhou Institute of Respiratory Disease, Guangdong, Guangzhou, China
The Second Affiliated Hospital of Hebei University, Shijiazhuang, Hebei, China
The First Affiliated Hospital of Zhengzhou University:, Zhengzhou, Henan, China
Shenyang Military Hospital, Shenyang, Liaoning, China
The Affiliated Hospital of Shenyang Medical University, Shenyang, Liaoning, China
The Affiliated Hospital of Ningxia Medical University, Yinchuang, Ningxia, China
Shangdong Yantaishan Hospital, Yantai, Shandong, 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 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
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
Zhejiang Shaoyifu Hospital, Hangzhou, Zhenjiang, China
Additional Information
Related publications: 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. 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. 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. 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. 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. 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.
Starting date: June 2002
Last updated: October 28, 2008
|