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

Sponsor

Beijing Chao Yang Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00799968

Collaborator

(none)

129

Enrollment

Locations

Arms

44.1

Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism Thromboembolism	Drug: Urokinase Drug: Urokinase	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

129 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

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 UK-12h group	Drug: Urokinase UK,bolus 4 400 U/kg followed by intravenous 2 200 U/kg•h for 12 hours Other Names: Urokinase,thrombolytic agent
Experimental: Group 2 UK-2h group	Drug: Urokinase UK,20 000U/kg continuously intravenous infusion for 2 hours Other Names: Urokinase,thrombolytic agent

Arm

Intervention/Treatment

Active Comparator: Group 1

UK-12h group

Drug: Urokinase

UK,bolus 4 400 U/kg followed by intravenous 2 200 U/kg•h for 12 hours

Other Names:

Urokinase,thrombolytic agent

Experimental: Group 2

UK-2h group

Drug: Urokinase

UK,20 000U/kg continuously intravenous infusion for 2 hours

Other Names:

Urokinase,thrombolytic agent

Outcome Measures

Primary Outcome Measures

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

The incidence of major or minor bleeding, death rate, and PTE recurrence at 14d after treatment. [14d]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

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 General Hospital of the Air-force PLA	Beijing	Beijing	China	100036
3	Beijing Fu Xing Hospital, Capital Medical University	Beijing	Beijing	China	100037
4	Beijing Naval General Hospital	Beijing	Beijing	China	100037
5	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
6	Peking University Third Hospital	Beijing	Beijing	China	100083
7	Beijing Hospital	Beijing	Beijing	China	100730
8	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing	China	100730
9	The First Affiliated Hospital Sun Yat-Sen University	Guangzhou	Guandong	China	510120
10	Guangzhou Institute of Respiratory Disease，Guangzhou Medical University	Guangzhou	Guangdong	China	510120
11	Shenzhen People's Hospital	Shenzhen	Guangdong	China	518020
12	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530027
13	The Second Affiliated Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050000
14	Tangshan Worker's Hospital, Hebei Medical University	Tangshan	Hebei	China	063000
15	The Affiliated Hospital of Hubei Coal University	Tangshan	Hebei	China	063000
16	Wuhan Union Hospital	Wuhan	Hubei	China	430022
17	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
18	The General Hospital of Shenyang Military Command	Shenyang	Liaoning	China	110016
19	Qilu Hospital Affiliated to Shandong University	Jinan	Shandong	China	250012
20	The Affiliated Hospital of Medical College Qingdao	Qingdao	Shandong	China	266003
21	Shangdong Yantaishan Hospital	Yantai	Shandong	China
22	The First Affiliated Hospital of Jining Medical College	Jinan	Shangdong	China
23	The First Affiliated Hospital of Qingdao University CHENG Zhao-zhong	Qingdao	Shangdong	China
24	The Fifth People's Hospital of Datong in ShanxiWANG;	Datong	Shanxi	China
25	The First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
26	The Second Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
27	Tianjin Thoracic Hospital	Tianjin	Tianjin	China	300051
28	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052
29	Xinjiang People's Hospital	Urumqi	Xinjiang	China	830001
30	Sir Run Run Shaw Hospital, Affiliated with Zhejiang University	Hangzhou	Zhejiang	China	310016
31	The First Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325000