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

Study Overview
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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.

Official Title
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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

Conditions
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Pulmonary Embolism, Thromboembolism

Intervention / Treatment
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* Drug: rt-PA
* Drug: rt-PA


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>rt-PA 100 mg continuous intravenous infusion for 2 hours | Drug: rt-PA<br>* rt-PA 100 mg continuous intravenous infusion for 2 hours<br>* Other names: Recombinant tissue plasminogen activator;|
| Experimental: group 2<br>rt-PA 50 mg continuous intravenous infusion for 2 hours | Drug: rt-PA<br>* rt-PA 50 mg continuous intravenous infusion for 2 hours<br>* Other names: Recombinant tissue plasminogen activator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major or minor bleeding |  | within 1st 14 days | 
| PE recurrence |  | within the 1st 14 days | 
| Death |  | within the 1st 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombolytic therapy, Recombinant tissue plasminogen activator, Efficacy, Safety