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

NCT ID: NCT00781378

Last Updated: 2008-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-06-30

Study Completion Date

2006-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pulmonary Embolism Thromboembolism

Keywords

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Thrombolytic therapy Recombinant tissue plasminogen activator Efficacy Safety

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Group 1

rt-PA 100 mg continuous intravenous infusion for 2 hours

Group Type ACTIVE_COMPARATOR

rt-PA

Intervention Type DRUG

rt-PA 100 mg continuous intravenous infusion for 2 hours

group 2

rt-PA 50 mg continuous intravenous infusion for 2 hours

Group Type EXPERIMENTAL

rt-PA

Intervention Type DRUG

rt-PA 50 mg continuous intravenous infusion for 2 hours

Interventions

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rt-PA

rt-PA 100 mg continuous intravenous infusion for 2 hours

Intervention Type DRUG

rt-PA

rt-PA 50 mg continuous intravenous infusion for 2 hours

Intervention Type DRUG

Other Intervention Names

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Recombinant tissue plasminogen activator Recombinant tissue plasminogen activator

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beijing Chao Yang Hospital

OTHER

Sponsor Role lead

Responsible Party

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Beijing Chao-Yang Hospital

Principal Investigators

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Chen WANG, Prof

Role: PRINCIPAL_INVESTIGATOR

Beijing Institute of Respiratory Medicine,Beijing Chao-Yang Hospital,Capital Medical University

Locations

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Beijing Chaoyang Hospital, Capital University of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Beijing University People's Hospital

Beijing, Beijing Municipality, China

Site Status

Peking Union Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

The Omni-hospital of Air-force

Beijing, Beijing Municipality, China

Site Status

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Site Status

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Site Status

Guangzhou Institute of Respiratory Disease

Guangdong, Guangzhou, China

Site Status

The Second Affiliated Hospital of Hebei University

Shijiazhuang, Hebei, China

Site Status

The First Affiliated Hospital of Zhengzhou University:

Zhengzhou, Henan, China

Site Status

Shenyang Military Hospital

Shenyang, Liaoning, China

Site Status

The Affiliated Hospital of Shenyang Medical University

Shenyang, Liaoning, China

Site Status

The Affiliated Hospital of Ningxia Medical University

Yinchuang, Ningxia, China

Site Status

Shangdong Yantaishan Hospital

Yantai, Shandong, China

Site Status

Qilu Hospital of Shandong University

Jinan, Shangdong, China

Site Status

The First Affiliated Hospital of Jining Medical College

Jinan, Shangdong, China

Site Status

The First Affiliated Hospital of Qingdao University CHENG Zhao-zhong

Qingdao, Shangdong, China

Site Status

Shanghai Hospital of Lung Disease

Shanghai, Shanghai Municipality, China

Site Status

Shanghai Ruijin Hospital HUANG Shao-guang

Shanghai, Shanghai Municipality, China

Site Status

The First Affiliated Hospital of Shanxi University

Taiyuan, Shanxi, China

Site Status

The Second Affiliated Hospital of Shanxi University

Taiyuan, Shanxi, China

Site Status

Tianjin Hospital of Medical Sciences

Tianjin, Tianjin Municipality, China

Site Status

The Affiliated Hospital of Wenzhou Medical College

Wenzhou, Zhejiang, China

Site Status

Zhejiang Shaoyifu Hospital

Hangzhou, Zhenjiang, China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 18261355 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17716753 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17705052 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17254482 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16796899 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15634378 (View on PubMed)

Wang C, Zhai Z, Yang Y, Wu Q, Cheng Z, Liang L, Dai H, Huang K, Lu W, Zhang Z, Cheng X, Shen YH; China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010 Feb;137(2):254-62. doi: 10.1378/chest.09-0765. Epub 2009 Sep 9.

Reference Type DERIVED
PMID: 19741062 (View on PubMed)

Other Identifiers

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2004BA703B07

Identifier Type: -

Identifier Source: secondary_id

2001BA703B13

Identifier Type: -

Identifier Source: org_study_id