The Treatment of Acute Deep Vein Thrombosis (DVT) of GSK576428 (Fondaparinux Sodium) in Japanese Patients

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The primary objective of this study is to evaluate the efficacy (as measured by the rate of recurrent symptomatic Venous Thromboembolism [VTE] (i.e., Pulmonary thromboembolism [PE] and Deep Vein Thrombosis [DVT])) and safety of GSK576428 as the initial treatment in subjects with acute symptomatic DVT in an open-label design.

Condition or disease	Intervention/treatment	Phase
Thrombosis, Venous	Drug: Fondaparinux sodium; Drug: unfractionated heparin (UFH)	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	39 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in the Treatment of Acute Deep Vein Thrombosis (DVT)
Study Start Date :	June 2008
Actual Primary Completion Date :	November 2009
Actual Study Completion Date :	November 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Fondaparinux	Drug: Fondaparinux sodium; The dose of Fondaparinux will be determined based on a subject's body weight (< 50 kg, 5 mg; 50 to 100 kg, 7.5 mg; >100 kg, 10 mg) and administered once daily by subcutaneous (SC) injection.; Other Name: GSK576428
unfractionated heparin	Drug: unfractionated heparin (UFH); UFH therapy will be started on Day 1 while adjusting activated partial thromboplastin time (aPTT) to maintain aPTT 1.5 to 2.5 times control.

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Recurrent or New Symptomatic Venous Thromboembolism (VTE) [ Time Frame: From Day 1 to Day 90 (±7 days) ]
   VTE (pulmonary thromboembolism [PE] and/or deep vein thrombosis [DVT]) was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE).

Secondary Outcome Measures :

1. Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) [ Time Frame: From Day 1 to Day 90 (±7 days) ]
   VTE (pulmonary thromboembolism [PE] and/or deep vein thrombosis [DVT]) was adjudicated blindly by the CIACE.
2. Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse Compared to Baseline [ Time Frame: Baseline, single day between Day 5 and Day 10 (the day when the medication [FPX or UFH] was finished /discontinued) (±1 day) ]
   Classifications of "Improved," "No change," or "Worse" were adjudicated blindly by the CIACE.
3. Total Perfusion Score at Baseline and Mean Change From Baseline at Day 5-10 [ Time Frame: Baseline, single day between Day 5 and Day 10 (the day when the medication [FPX or UFH] was finished /discontinued) (±1 day) ]
   Change from baseline was calculated as the score on the day medication was finished/discontinued (anywhere from Day 5 to Day 10) minus the baseline score. The perfusion score (0: no perfusion; 0.25, 0.5, 0.75, 1: normal) in each of the six lobes of the lung was adjudicated blindly by the CIACE. Total perfusion score (r) was calculated as: r = (0.25 x right lower lobe) + (0.12 x right middle lobe) + (0.18 x right upper lobe) + (0.20 x left lower lobe) + (0.12 x lingula) + (0.13 x left upper lobe).
4. Percentage of Participants With a Bleeding Event [ Time Frame: Initial treatment period (from the first dose of FPX/UFH to N days after the last dose of FPX/UFH; specified based on creatinine clearance [CLcr]; N=3, CLcr >=50 mL/min; N=4, 30 =< CLcr < 50 mL/min; N=9, CLcr < 30 mL/min). ]
   Bleeding events (major bleeding [clinically overt bleeding with fatality, location in a critical organ, a fall in hemoglobin >=2 grams (g)/deciliter (dL), or a transfusion >=2 units]; minor bleeding [clinically overt bleeding and not adjudicated as major bleeding], and no bleeding) were adjudicated blindly by the Central Independent Adjudication Committee of Safety (CIACS).

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of acute proximal DVT based on contrast-enhanced Multi detector-row CT (MDCT) (not more than 10 days after the onset of the symptoms of DVT)
• Age:20 years
• Gender: No restriction
• Hospitalization status: Subjects who are able to stay at the hospital at least during the initial treatment period
• Written informed consent from the subject him/herself or his/her legally acceptable representative. Written informed consent from the subject's legally acceptable representative must be obtained if the subject is incapable of giving consent

Exclusion Criteria:

• Symptomatic PE
• Requirement for surgical thrombectomy, catheter intervention and thrombolytic therapy for the current DVT
• Subjects (for example, with free-floating thrombus in the femoral vein or ilium by MDCT at screening) for whom insertion of inferior vena cava filter is indicated or subjects in whom inferior vena cava filter is present
• Anticoagulant therapy for at least 24 hours to treat the current episode prior to entry into the study
• Active, clinically significant bleeding
• Thrombocytopenia (platelet count <10×10⁴/µL at screening)
• Concurrent conditions with bleeding risk (e.g., ulcer of the gastrointestinal tract, diverticulitis of the gastrointestinal tract, colitis, acute bacterial endocarditis, severe hypertension, or severe diabetes) or bleeding tendency
• Severe hepatic disorder
• Known hypersensitivity to heparin, low-molecular-weight heparin (LMWH) or warfarin
• Previous history of cerebral hemorrhage
• Brain, spinal, or ophthalmological surgery within 3 months prior to entry into this study
• Previous history of Heparin-induced thrombocytopenia
• Patients for whom anticoagulant therapy is contraindicated or who cannot be taken off anticoagulant therapy due to coexistent condition (e.g. prosthetic heart valve implant)
• Severe renal disorder (serum creatinine >2.0 mg/dL [180 µmol/L] at screening) in a well hydrated subject
• QT interval prolonged (QT interval corrected by Bazett's formula [QTcB] ≥450 msec; for patients with bundle branch block QTcB ≥480 msec) at screening
• Documented hypersensitivity to contrast media
• Use of any contraindicated drug that cannot be combined with the injection of contrast medium [e.g., antihyperglycemics, such as biguanides (metformin hydrochloride, buformin hydrochloride)]
• Participation in any other therapeutic drug study or a clinical study within 6 months prior to entry into this study
• Previous participation in a study of GSK576428 [Fondaparinux Sodium; including the studies of Org31540/SR90107A (ex-project code)] or previous exposure to the therapeutic dose of GSK576428
• Drug or alcohol abuse
• Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
• Recent surgery within 3 days prior to entry into the study
• Life expectancy <3 months
• Pregnant women, nursing mothers, women who may be pregnant, or women contemplating pregnancy during the study period
• Others whom the investigator or subinvestigator considers not eligible for the study

Contacts and Locations

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Locations

Japan
GSK Investigational Site
Aichi, Japan, 440-8510
GSK Investigational Site
Fukuoka, Japan, 802-8555
GSK Investigational Site
Gunma, Japan, 370-0829
GSK Investigational Site
Gunma, Japan, 371-8511
GSK Investigational Site
Hiroshima, Japan, 720-8520
GSK Investigational Site
Hiroshima, Japan, 739-0651
GSK Investigational Site
Hokkaido, Japan, 006-8555
GSK Investigational Site
Hokkaido, Japan, 060-8543
GSK Investigational Site
Hokkaido, Japan, 060-8648
GSK Investigational Site
Hyogo, Japan, 654-0155
GSK Investigational Site
Ibaraki, Japan, 305-8576
GSK Investigational Site
Ibaraki, Japan, 311-3193
GSK Investigational Site
Kagoshima, Japan, 892-0853
GSK Investigational Site
Kanagawa, Japan, 245-8575
GSK Investigational Site
Kumamoto, Japan, 860-0008
GSK Investigational Site
Kumamoto, Japan, 860-8556
GSK Investigational Site
Mie, Japan, 514-8507
GSK Investigational Site
Nagano, Japan, 399-0021
GSK Investigational Site
Nagasaki, Japan, 859-3615
GSK Investigational Site
Niigata, Japan, 951-8520
GSK Investigational Site
Okayama, Japan, 701-1192
GSK Investigational Site
Shizuoka, Japan, 430-8558
GSK Investigational Site
Shizuoka, Japan, 438-8550
GSK Investigational Site
Tokyo, Japan, 113-8655

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Dataset Specification 

Identifier: 111436
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 111436
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 111436
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

Nakamura M, Okano Y, Minamiguchi H, Munemasa M, Sonoda M, Yamada N, Hanzawa K, Aoyagi N, Tsujimoto H, Sarai N, Nakajima H, Kunieda T. Multidetector-row computed tomography-based clinical assessment of fondaparinux for treatment of acute pulmonary embolism and acute deep vein thrombosis in Japanese patients. Circ J. 2011;75(6):1424-32. Epub 2011 Apr 22.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00911157 History of Changes
Other Study ID Numbers:	111436
First Posted:	June 1, 2009
Results First Posted:	June 10, 2010
Last Update Posted:	November 23, 2016
Last Verified:	October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

Pulmonary thromboembolism; contrast-enhanced MDCT; Deep Vein Thrombosis; Fondaparinux sodium

Additional relevant MeSH terms:

Thrombosis; Venous Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Calcium heparin; Fondaparinux; PENTA; Heparin	Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors