Nadroparin for the Initial Treatment of Pulmonary Thromboembolism

Pulmonary Embolism Clinical Trial

— NATSPUTE  

Official title:

Efficacy and Safety of Body Weight Adjusted Nadroparin vs Standard Unfractionated Heparin for the Initial Treatment of Pulmonary Thromboembolism：a Multi-Centre, Randomised Controlled Trial in China

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00796692
• Other study ID #: 2004BA703B07
• Secondary ID: 2001BA703B13
• Status: Completed
• Phase: Phase 4
• First received: November 20, 2008
• Last updated: November 21, 2008
• Start date: June 2002
• Est. completion date: February 2006

Study information

• Verified date: November 2008
• Source: Beijing Chao Yang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Low-molecular-weight heparin (LWMH) appears to be at least as effective and safe as standard, unfractionated heparin (UFH)for the treatment of patients with deep vein thrombosis(DVT) and may also be so in patients with pulmonary thromboembolism (PTE). Only limited data are available on the evaluation of body weight adjusted LWMH and standard UFH for the initial treatment of PTE in Chinese population. The aim of this study is to determine whether body weight-adjusted, subcutaneous Nadroparin is as effective and safe as UFH for treatment of patients with objectively documented PTE.

Description:

Low-molecular-weight heparin (LWMH) appears to be at least as effective and safe as standard, unfractionated heparin (UFH)for the treatment of patients with deep vein thrombosis(DVT) and may also be so in patients with pulmonary thromboembolism (PTE). Only limited data are available on the evaluation of body weight adjusted LWMH and standard UFH for the initial treatment of PTE in Chinese population.

The aim of this study is to determine whether body weight-adjusted, subcutaneous Nadroparin is as effective and safe as UFH for treatment of patients with objectively documented PTE.

An open-label, adjudicator-blinded, randomized controlled trial of patients with symptomatic non-massive PTE from 37 major hospitals in China is conducted . Intravenous UFH was administered received an initial bolus dose of 80 IU/kg, followed by a continuous infusion at an initial rate of 18 IU/kg /hour. The dose was subsequently adjusted by activated partial thromboplastin time (APTT) monitoring. LMWH (nadroparin) was administered subcutaneously at a dose of 86 anti-factor Xa IU/kg every 12 hours.

Both treatments were overlapped with at least 3 months of warfarin therapy. Main outcome measures were combined end point of clinical effect, image improvement,Recurrent venous thromboembolism(VTE), major bleeding, and death within 14 days and 3 months of randomization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 274
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18 to 75 years of age

• Symptomatic non massive PTE confirmed either by a high probability ventilation-perfusion lung scanning (V/Q scan) or by the presence of intraluminal filling defect on spiral computed tomographic pulmonary angiography (CTPA)

• Haemodynamic stabile, anatomic obstruction no more than 2 lobes on CTPA, or defect no more than 7 segments on V/Q scan,and normal right ventricular function

• Symptoms within 15 days

• Written informed consent obtained before randomization.

Exclusion Criteria:

• Unfractioned heparin anticoagulation for more than 36 hours prior enrollment,

• Massive PTE or sub-massive PTE requiring thrombolytic therapy or pulmonary embolectomy; Active bleeding or disorders contraindicating anticoagulant therapy

• Chronic thromboembolism pulmonary hypertension(CTEPH) without evidence of recent episode; Severe hepatic or renal failure

• Allergy to heparin, other components of Tinzaparin or acenocoumarol,

• Pregnant status;a life expectancy of less than 3 months;

• Previous thrombocytopenia induced by heparin

• Thrombocytopenia < 100000/mm3,

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Embolism
• Thromboembolism
• Thrombosis
• Vascular Diseases

Intervention

Drug:
• Nadroparin
LMWH is given with a weight adjusted dose of 86 international anti-factor Xa units of nadroparin (Fraxiparine) per kilogram of body weight(86 anti-factor Xa IU/kg) subcutaneously every 12 hours,which will be used at least 5-7 days.
• Unfractionated heparin(UFH)
UFH is received with an initial bolus dose of 80 IU per kilogram, followed by a continuous intravenous infusion at an initial rate of 18 IU per kilogram per hour. The dose is subsequently adjusted so that the activated partial thromboplastin time (APTT) would be 1.5 to 2.5 times the control value in normal subjects. The tests are performed 4 hours after the start of treatment, whenever a sub-therapeutic APTT had been measured after a dose adjustment, and otherwise daily.UFH will be used at least 5-7 days.

Locations

Country	Name	City	State
China	Liaoning Angang Tiedong Hospital	Anshan	Liaoning
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing General Hospital of the Air-force PLA	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Beijing Naval General Hospital	Beijing	Beijing
China	Beijing No 6 Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Shanxi Datong 5th Hospital	Datong	Shanxi
China	Guangzhou Institute of Respiratory Disease,Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital Sun Yat-Sen University	Guangzhou	Guandong
China	The Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, Affiliated with Zhejiang University	Hangzhou	Zhejiang
China	Qilu Hospital Affiliated to Shandong University	Jinan	Shandong
China	The Affiliated Hospital of Medical College Jining	Jining	Shandong
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The Affiliated Hospital of Medical College Qingdao	Qingdao	Shandong
China	Shanghai Changhai Hospital	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital(8)	Shanghai	Shanghai
China	Shanghai Ruijin Hospital	Shanghai	Shanghai
China	The Affiliated Hospital of Shenyang Medical University	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	The General Hospital of Shenyang Military Command	Shenyang	Liaoning
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	The Second Affiliated Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	The Second Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tangshan Worker's Hospital, Hebei Medical University	Tangshan	Hebei
China	The Affiliated Hospital of Hubei Coal University	Tangshan	Hebei
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tianjin Thoracic Hospital	Tianjin	Tianjin
China	Xinjiang People's Hospital	Urumqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Wuhan Union Hospital	Wuhan	Hubei
China	Shandong Yantaishan Hospital	Yantai	Shandong
China	The Affiliated Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

Liu CP, Lu WX, Liu WG, Chen HW, Wang C. [The low molecular weight heparin on rat pulmonary surfactant associated protein A of acute pulmonary embolism]. Zhonghua Yi Xue Za Zhi. 2007 Mar 6;87(9):634-6. Chinese. — View Citation

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. — View Citation

Pang BS, Wang C, Luo Q, Zhang LM, Zhu M, Mao YL, Huang XX, Guo WJ. [Study of the function of coagulation, fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Jun;27(6):381-4. Chinese. — View Citation

Qin ZQ, Wang C. [Comparison of thrombolysis and anticoagulation in pulmonary thromboembolism: a meta-analysis]. Zhonghua Jie He He Hu Xi Za Zhi. 2003 Dec;26(12):772-5. Chinese. — View Citation

Sun KK, Wang C, Guli XT, Luo Q. [Risk factors and clinical features of deep venous thrombosis: a report of 388 cases]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Nov;27(11):727-30. Chinese. — View Citation

Zai ZG, Wang C. [Advances in the study of pulmonary thromboembolism]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Jan;27(1):14-8. Review. Chinese. — View Citation

Zhai ZG, Wang C, Liu YM, Qin ZQ. [Comparison of unfractionated heparin and low molecular weight heparin in pulmonary thromboembolism: meta-analysis]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2004 Jun;26(3):221-6. Chinese. — View Citation

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. Epub 2007 Aug 21. — View Citation

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. Epub 2007 Aug 22. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical and image(including V/Q scan and CTPA) improvement		Time Frame: 14days	No
Secondary	Recurrent venous thromboembolism(VTE), major bleeding death Heparin-induced thrombocytopenia		3 months	Yes