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

Sponsor

Beijing Chao Yang Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00781378

Collaborator

(none)

118

Enrollment

Locations

Arms

44.1

Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism Thromboembolism	Drug: rt-PA Drug: rt-PA	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

118 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Feb 1, 2006

Actual Study Completion Date :

Feb 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 rt-PA 100 mg continuous intravenous infusion for 2 hours	Drug: rt-PA rt-PA 100 mg continuous intravenous infusion for 2 hours Other Names: Recombinant tissue plasminogen activator
Experimental: group 2 rt-PA 50 mg continuous intravenous infusion for 2 hours	Drug: rt-PA rt-PA 50 mg continuous intravenous infusion for 2 hours Other Names: Recombinant tissue plasminogen activator

Arm

Intervention/Treatment

Active Comparator: Group 1

rt-PA 100 mg continuous intravenous infusion for 2 hours

Drug: rt-PA

rt-PA 100 mg continuous intravenous infusion for 2 hours

Other Names:

Recombinant tissue plasminogen activator

Experimental: group 2

rt-PA 50 mg continuous intravenous infusion for 2 hours

Drug: rt-PA

rt-PA 50 mg continuous intravenous infusion for 2 hours

Other Names:

Recombinant tissue plasminogen activator

Outcome Measures

Primary Outcome Measures

The improvement of the right hart function on echocardiograms [within the 1st 14 days]
Perfusion defect score of lung V/Q scans [within the 1st 14 days]
Quantitative computed tomographic pulmonary angiography (CTPA) score on 2d, 14d after treatment. [within the 1st 14 days]

Secondary Outcome Measures

Major or minor bleeding [within 1st 14 days]
PE recurrence [within the 1st 14 days]
Death [within the 1st 14 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Chaoyang Hospital, Capital University of Medical Sciences	Beijing	Beijing	China	100020
2	Beijing University People's Hospital	Beijing	Beijing	China
3	Peking Union Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing	China
4	The Omni-hospital of Air-force	Beijing	Beijing	China
5	Shenzhen People's Hospital	Shenzhen	Guangdong	China
6	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China
7	Guangzhou Institute of Respiratory Disease	Guangdong	Guangzhou	China
8	The Second Affiliated Hospital of Hebei University	Shijiazhuang	Hebei	China
9	The First Affiliated Hospital of Zhengzhou University:	Zhengzhou	Henan	China
10	Shenyang Military Hospital	Shenyang	Liaoning	China
11	The Affiliated Hospital of Shenyang Medical University	Shenyang	Liaoning	China
12	The Affiliated Hospital of Ningxia Medical University	Yinchuang	Ningxia	China
13	Shangdong Yantaishan Hospital	Yantai	Shandong	China
14	Qilu Hospital of Shandong University	Jinan	Shangdong	China
15	The First Affiliated Hospital of Jining Medical College	Jinan	Shangdong	China
16	The First Affiliated Hospital of Qingdao University CHENG Zhao-zhong	Qingdao	Shangdong	China
17	Shanghai Hospital of Lung Disease	Shanghai	Shanghai	China
18	Shanghai Ruijin Hospital HUANG Shao-guang	Shanghai	Shanghai	China
19	The First Affiliated Hospital of Shanxi University	Tai-yuan	Shanxi	China
20	The Second Affiliated Hospital of Shanxi University	Tai-yuan	Shanxi	China
21	Tianjin Hospital of Medical Sciences	Tianjin	Tianjin	China
22	The Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China
23	Zhejiang Shaoyifu Hospital	Hangzhou	Zhenjiang	China