NATSPUTE: Nadroparin for the Initial Treatment of Pulmonary Thromboembolism

Sponsor

Beijing Chao Yang Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00796692

Collaborator

(none)

274

Enrollment

Locations

Arms

44.1

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism Thromboembolism Vascular Diseases Thrombosis	Drug: Nadroparin Drug: Unfractionated heparin(UFH)	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

274 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 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
Experimental: Group 2 Low molecular weight heparin	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. Other Names: Low moleculor weight hepatin
Active Comparator: Group 1 Unfractionated heparin(UFH)	Drug: 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. Other Names: Standard Unfractionated heparin

Arm

Intervention/Treatment

Experimental: Group 2

Low molecular weight heparin

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.

Other Names:

Low moleculor weight hepatin

Active Comparator: Group 1

Unfractionated heparin(UFH)

Drug: 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.

Other Names:

Standard Unfractionated heparin

Outcome Measures

Primary Outcome Measures

Clinical and image(including V/Q scan and CTPA) improvement [Time Frame: 14days]

Secondary Outcome Measures

Recurrent venous thromboembolism(VTE), major bleeding death Heparin-induced thrombocytopenia [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University First Hospital	Beijing	Beijing	China	100034
2	Beijing General Hospital of the Air-force PLA	Beijing	Beijing	China	100036
3	Beijing Naval General Hospital	Beijing	Beijing	China	100037
4	Peking University People's Hospital	Beijing	Beijing	China	100044
5	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
6	Beijing No 6 Hospital	Beijing	Beijing	China	100083
7	Peking University Third Hospital	Beijing	Beijing	China	100083
8	Beijing Hospital	Beijing	Beijing	China	100730
9	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing	China	100730
10	The First Affiliated Hospital Sun Yat-Sen University	Guangzhou	Guandong	China	510120
11	Guangzhou Institute of Respiratory Disease，Guangzhou Medical University	Guangzhou	Guangdong	China	510120
12	The Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510630
13	Shenzhen People's Hospital	Shenzhen	Guangdong	China	518020
14	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530027
15	The Second Affiliated Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050000
16	Tangshan Worker's Hospital, Hebei Medical University	Tangshan	Hebei	China	063000
17	The Affiliated Hospital of Hubei Coal University	Tangshan	Hebei	China	063000
18	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450052
19	Wuhan Union Hospital	Wuhan	Hubei	China	430022
20	Liaoning Angang Tiedong Hospital	Anshan	Liaoning	China	114002
21	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
22	The General Hospital of Shenyang Military Command	Shenyang	Liaoning	China	110016
23	The Affiliated Hospital of Shenyang Medical University	Shenyang	Liaoning	China	110024
24	The Affiliated Hospital of Ningxia Medical University	Yinchuan	Ningxia	China	750004
25	Qilu Hospital Affiliated to Shandong University	Jinan	Shandong	China	250012
26	The Affiliated Hospital of Medical College Jining	Jining	Shandong	China	272029
27	The Affiliated Hospital of Medical College Qingdao	Qingdao	Shandong	China	266003
28	Shandong Yantaishan Hospital	Yantai	Shandong	China	264001
29	Shanghai Ruijin Hospital	Shanghai	Shanghai	China	200025
30	Shanghai Changhai Hospital	Shanghai	Shanghai	China	200433
31	Shanghai Pulmonary Hospital(8)	Shanghai	Shanghai	China	200433
32	Shanxi Datong 5th Hospital	Datong	Shanxi	China	037006
33	The First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
34	The Second Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
35	Tianjin Thoracic Hospital	Tianjin	Tianjin	China	300051
36	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052
37	Xinjiang People's Hospital	Urumqi	Xinjiang	China	830001
38	Sir Run Run Shaw Hospital, Affiliated with Zhejiang University	Hangzhou	Zhejiang	China	310016
39	The First Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325000