12-h and 2-h Urokinase Regimes of Pulmonary Thromboembolism in China

Study Overview
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Brief Summary
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Comparative trials of urokinase (UK) for 12 hours（UK-12h）or 24 hours (UK-24h) have produced similar results in acute pulmonary thromboembolism (PTE) thrombolysis. It is unclear whether the infusion time can be reduced further. The aim of this study was to investigate the efficacy and safety of weight adjusted dosage of UK-2h (20 000 IU/Kg) regime with the Uk-12h regime in selected patients with PTE in Chinese population.

Detailed Description
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Pulmonary thromboembolism (PTE), a frequent life-threatening complication of deep vein thrombosis (DVT), is often underestimated and under diagnosed . Effective early treatment will decrease the mortality, reverse right heart dysfunction and reduce risk of chronic thromboembolic pulmonary hypertension (CTEPH) or post-thrombotic syndrome (PTS). Thrombolysis has proved to be the most rapid and effective therapy to reduce the obstruction of pulmonary circulation and normalize hemodynamic parameters. The ultimate goals of thombolytic therapy for this disease are to minimize early morbidity and mortality and to prevent recurrence without provoking excessive bleeding. Currently, the choice of thrombolytic agents and regimens (either UK or rt-PA) is mostly based on personal or regional preferences. A loading dose of UK 4400 IU/kg followed by 2200 IU/kg/hour for 12 hours (UK-12h), or rt-PA 100 mg infusion over 2 hours are recommended for acute PTE treatment. However, increasing evidence suggest that UK infusion can be more concentrated and time can be further reduced. 100 mg/2 h of rt-PA and a novel dosing regimen of UK(3 million U/2 h) had been compared. The results indicated that a 2-h regimen of rt-PA and 2h UK exhibited similar efficacy and safety for treatment of acute PTE. UK-2h(20 000U/Kg) regimen combined with low molecular weight heparin (LMWH) had been used in Chinese population.No severe bleeding and allergic reaction occurred in the thrombolytic group. This dosage is much lower than that used by Goldhaber et al, but the efficacy was prominent. Until now,no study have been reported to compared UK-2h(20 000U/Kg) regimen with other UK regimens(such as UK-12h). A relative lower dosage of UK 2-h regimen with body weight adjusted may be an alternative choice for treating PTE patients in Chinese population.Considering lower cost and convenience of this regimen, the efficacy and safety between UK-2h regimen(20 000U/Kg) and ACCP-approved UK-12h regimen for treating acute PTE will be compared.The study is conducted on patients with massive PTE with shock or hypotension and/or if without shock or hypotension but with right ventricular dysfunction. The clinical efficacy, emboli dissolving efficacy and safety will be evaluated.

Official Title
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Efficacy and Safety Evaluation of 12-h and 2-h Urokinase Regimes 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: Urokinase
* Drug: Urokinase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PTE confirmed either by a high probability ventilation-perfusion lung scanning (V/Q scan) or by CTPA. massive PTE patients with haemodynamic instability and/or cardiogenic shock Anatomic obstruction more than 2 lobes on CTPA and/or defect more than 7 segments on V/Q scan with evidence of right ventricular dysfunction (RVD) and pulmonary hypertension on echocardiography Symptoms within 15 days Written informed consent was obtained from all the patients before randomization Exclusion Criteria: Received parenteral heparin for more than 72 hours Known allergic to urokinase Thrombolytic contraindications such as: 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>UK-12h group | Drug: Urokinase<br>* UK,bolus 4 400 U/kg followed by intravenous 2 200 U/kg•h for 12 hours<br>* Other names: Urokinase,thrombolytic agent;|
| Experimental: Group 2<br>UK-2h group | Drug: Urokinase<br>* UK,20 000U/kg continuously intravenous infusion for 2 hours<br>* Other names: Urokinase,thrombolytic agent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The improvement of the right ventricular function , perfusion defect score on lung V/Q scans or quantitative computed tomographic pulmonary angiography (CTPA) score. |  | 14d | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of major or minor bleeding, death rate, and PTE recurrence at 14d after treatment. |  | 14d | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombolytic therapy, Urokinase, Efficacy, Safety