The Treatment of Acute Pulmonary Thromboembolism (PE) of GSK576428 (Fondaparinux Sodium) in Japanese Patients

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00981409
First received: September 3, 2009
Last updated: July 7, 2011
Last verified: July 2011
  Purpose

The primary objective 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 PE in an open-label design.


Condition Intervention Phase
Acute Pulmonary Thromboembolism
Embolism, Pulmonary
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 Pulmonary Thromboembolism (PE)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The 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 thromboembolism [DVT]) was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE).


Secondary Outcome Measures:
  • The Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic Venous Thromboembolism (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 thromboembolism [DVT]) was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE).

  • The Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse [ Time Frame: Baseline, Days 5-10 (the day when the medication [FPX or UFH] was finished /discontinued) (+/-1) ] [ Designated as safety issue: No ]
    "Improved," "No change," or "Worse" was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE). Each category is adjudicated by comparison with the perfusion score at baseline by the CIACE.

  • Total Perfusion Score at Baseline and Mean Change From Baseline at Days 5-10 [ Time Frame: Baseline, Days 5-10 (the day when the medication [FPX or UFH] was finished /discontinued) (+/-1) ] [ Designated as safety issue: No ]
    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 Central Independent Adjudication Committee of Efficacy (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).

  • The Percentage of Participants With a Bleeding Event [ Time Frame: FPX or UFH treatment period (Days 5-10, on average) ] [ Designated as safety issue: Yes ]
    Bleeding events (major bleeding [clinically overt bleeding with: fatality, location in critical organ, a fall in hemoglobin >=2 g/dL, or a transfusion >=2 units], minor bleeding [clinically overt bleeding and not adjudicated as major bleeding]) were adjudicated blindly by the Central Independent Adjudication Committee of Safety (CIACS).


Enrollment: 41
Study Start Date: July 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (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:

  • Subjects with a confirmed diagnosis (by Multi detector-row CT [MDCT]) of acute symptomatic PE who are hemodynamically stable (i.e., the condition where anticoagulant therapy alone are indicated) (the time from onset should be no longer than 5 days, and subjects with or without symptomatic DVT are eligible)
  • Age: >=20 years
  • Gender: No restriction Female subjects must either be of non-childbearing potential (post-menopausal >1 year, hysterectomy, or sterilization), or of childbearing potential, has a negative pregnancy test at screening, and agree to use contraception throughout the study period.
  • 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:

  • Shock or hemodynamic instability*.

    *: Defined as shock or decreased blood pressure (systolic blood pressure <90 mmHg or >=40 mmHg) lasting for at least 15 minutes and does not represent hemodynamically unstable conditions due to newly emergent arrhythmia, dehydration or sepsis.

  • Right cardiac function failure detected by echocardiography at screening.
  • Requirement for surgical thrombectomy, catheter intervention and thrombolytic therapy for the current PE.
  • 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.
  • Prior to entry into the study, therapeutic dosage of anticoagulants for more than 24 hours to treat the current episode.
  • 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.

    *: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg

  • 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
  • Documented hypersensitivity to contrast media
  • Use of any contraindicated drug that cannot be combined with the injection of contrast medium [e.g., antihyperglycemic metformin hydrochloride (Glycoran®, Melbin®)]
  • 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
  • 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: NCT00981409

Locations
Japan
GSK Investigational Site
Fukuoka, Japan, 802-8555
GSK Investigational Site
Gunma, Japan, 370-0829
GSK Investigational Site
Gunma, Japan, 371-8511
GSK Investigational Site
Hokkaido, Japan, 060-8648
GSK Investigational Site
Ibaraki, Japan, 311-3193
GSK Investigational Site
Kagoshima, Japan, 892-0853
GSK Investigational Site
Kumamoto, Japan, 860-0008
GSK Investigational Site
Kumamoto, Japan, 860-8556
GSK Investigational Site
Mie, Japan, 514-8507
GSK Investigational Site
Nagasaki, Japan, 859-3615
GSK Investigational Site
Niigata, Japan, 951-8520
GSK Investigational Site
Okayama, Japan, 701-1192
GSK Investigational Site
Osaka, Japan, 530-8480
GSK Investigational Site
Osaka, Japan, 540-0006
GSK Investigational Site
Osaka, Japan, 565-8565
GSK Investigational Site
Saitama, Japan, 351-0102
GSK Investigational Site
Tokyo, Japan, 160-8582
GSK Investigational Site
Tokyo, Japan, 180-8610
GSK Investigational Site
Tokyo, Japan, 104-8560
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: NCT00981409     History of Changes
Other Study ID Numbers: 106206
Study First Received: September 3, 2009
Results First Received: October 14, 2009
Last Updated: July 7, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Fondaparinux sodium
contrast-enhanced MDCT
Deep Vein Thrombosis
Pulmonary thromboembolism

Additional relevant MeSH terms:
Thromboembolism
Pulmonary Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Lung Diseases
Respiratory Tract Diseases
Embolism
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 16, 2014