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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00911157
First received: May 28, 2009
Last updated: March 17, 2011
Last verified: March 2011
  Purpose

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 Intervention Phase
Thrombosis, Venous
Acute Deep Vein Thrombosis
Drug: Fondaparinux sodium
Drug: unfractionated heparin (UFH)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in the Treatment of Acute Deep Vein Thrombosis (DVT)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percentage of Participants With Recurrent or New Symptomatic Venous Thromboembolism (VTE) [ Time Frame: From Day 1 to Day 90 (±7 days) ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic VTE (by Type) [ Time Frame: From Day 1 to Day 90 (±7 days) ] [ Designated as safety issue: No ]
    VTE (pulmonary thromboembolism [PE] and/or deep vein thrombosis [DVT]) was adjudicated blindly by the CIACE.

  • 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) ] [ Designated as safety issue: No ]
    Classifications of "Improved," "No change," or "Worse" were adjudicated blindly by the CIACE.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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). ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 39
Study Start Date: June 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00911157

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
Hiroshima, Japan, 720-8520
GSK Investigational Site
Hiroshima, Japan, 739-0651
GSK Investigational Site
Hokkaido, Japan, 006-8555
GSK Investigational Site
Ibaraki, Japan, 311-3193
GSK Investigational Site
Ibaraki, Japan, 305-8576
GSK Investigational Site
Kagoshima, Japan, 892-0853
GSK Investigational Site
Kanagawa, Japan, 245-8575
GSK Investigational Site
Kumamoto, Japan, 860-8556
GSK Investigational Site
Kumamoto, Japan, 860-0008
GSK Investigational Site
Mie, Japan, 514-8507
GSK Investigational Site
Niigata, Japan, 951-8520
GSK Investigational Site
Okayama, Japan, 701-1192
GSK Investigational Site
Shizuoka, Japan, 438-8550
GSK Investigational Site
Shizuoka, Japan, 430-8558
GSK Investigational Site
Tokyo, Japan, 113-8655
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00911157     History of Changes
Other Study ID Numbers: 111436
Study First Received: May 28, 2009
Results First Received: May 13, 2010
Last Updated: March 17, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

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
Fondaparinux
PENTA
Calcium heparin
Heparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014