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

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in the Treatment of Acute Deep Vein Thrombosis (DVT)

Conditions
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Thrombosis, Venous

Intervention / Treatment
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* Drug: Fondaparinux sodium
* Drug: unfractionated heparin (UFH)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fondaparinux<br> | Drug: Fondaparinux sodium<br>* 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.<br>* Other names: GSK576428;|
| Other: unfractionated heparin<br> | Drug: unfractionated heparin (UFH)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) | VTE (pulmonary thromboembolism [PE] and/or deep vein thrombosis [DVT]) was adjudicated blindly by the CIACE. | From Day 1 to Day 90 (±7 days) | 
| Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse Compared to Baseline | Classifications of Improved, No change, or Worse were adjudicated blindly by the CIACE. | Baseline, single day between Day 5 and Day 10 (the day when the medication [FPX or UFH] was finished /discontinued) (±1 day) | 
| Total Perfusion Score at Baseline and Mean Change From Baseline at Day 5-10 | 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). | Baseline, single day between Day 5 and Day 10 (the day when the medication [FPX or UFH] was finished /discontinued) (±1 day) | 
| Percentage of Participants With a Bleeding Event | 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). | 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary thromboembolism, contrast-enhanced MDCT, Deep Vein Thrombosis, Fondaparinux sodium