Clinical trial NCT00796692: Nadroparin for the Initial Treatment of Pulmonary Thromboembolism
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Embolism
Thromboembolism
Vascular Diseases
Thrombosis
Keywords: Heparin
Low molecular weight heparin
Safety
Efficacy
Cost effective
Lead sponsor: Beijing Chao Yang Hospital
Sponsor class: OTHER
First posted: 2008-11-24
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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,

Primary outcomes:
measure: Clinical and image(including V/Q scan and CTPA) improvement
timeFrame: Time Frame: 14days
Secondary outcomes:
measure: Recurrent venous thromboembolism(VTE), major bleeding death Heparin-induced thrombocytopenia
timeFrame: 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing General Hospital of the Air-force PLA
state: Beijing
city: Beijing
country: China
facility: Beijing Naval General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing No 6 Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital Sun Yat-Sen University
state: Guandong
city: Guangzhou
country: China
facility: Guangzhou Institute of Respiratory Disease，Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: The Second Affiliated Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Tangshan Worker's Hospital, Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: The Affiliated Hospital of Hubei Coal University
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Anshan
country: China
facility: Liaoning Angang Tiedong Hospital
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military Command
state: Liaoning
city: Shenyang
country: China
facility: The Affiliated Hospital of Shenyang Medical University
state: Liaoning
city: Yinchuan
country: China
facility: The Affiliated Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Qilu Hospital Affiliated to Shandong University
state: Shandong
city: Jining
country: China
facility: The Affiliated Hospital of Medical College Jining
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Medical College Qingdao
state: Shandong
city: Yantai
country: China
facility: Shandong Yantaishan Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital(8)
state: Shanghai
city: Datong
country: China
facility: Shanxi Datong 5th Hospital
state: Shanxi
city: Taiyuan
country: China
facility: The First Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: The Second Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Thoracic Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Urumqi
country: China
facility: Xinjiang People's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Affiliated with Zhejiang University
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical College
state: Zhejiang
Study officials:
affiliation: Beijing Institute of Respiratory Medicine,Beijing Chao Yang Hospital
name: Chen WANG, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. doi: 10.1016/j.ijcard.2007.06.093. Epub 2007 Aug 22.
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. doi: 10.1007/s11239-007-0087-8. Epub 2007 Aug 21.
citation: 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.
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.
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.
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.
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.
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. No abstract available. Chinese.
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.