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

Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in the Treatment of Acute Pulmonary Thromboembolism (PE)

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.

Study Overview

• Status: Completed
• Conditions: Embolism, Pulmonary
• Intervention / Treatment: Drug: Fondaparinux sodium; Drug: unfractionated heparin (UFH)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 440-8510
    • GSK Investigational Site
  • Chiba, Japan, 260-8677
    • 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
  • Hokkaido, Japan, 060-8543
    • 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
  • Kumamoto, Japan, 860-8556
    • GSK Investigational Site
  • Kumamoto, Japan, 860-0008
    • GSK Investigational Site
  • Mie, Japan, 514-8507
    • GSK Investigational Site
  • Nagano, Japan, 390-8621
    • 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, 565-8565
    • GSK Investigational Site
  • Osaka, Japan, 530-8480
    • GSK Investigational Site
  • Osaka, Japan, 540-0006
    • GSK Investigational Site
  • Saitama, Japan, 351-0102
    • GSK Investigational Site
  • Tokyo, Japan, 160-8582
    • GSK Investigational Site
  • Tokyo, Japan, 113-8655
    • GSK Investigational Site
  • Tokyo, Japan, 113-8603
    • GSK Investigational Site
  • Tokyo, Japan, 104-8560
    • GSK Investigational Site
  • Tokyo, Japan, 180-8610
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: GSK576428
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants With Recurrent or New Symptomatic Venous Thromboembolism (VTE)	VTE (pulmonary thromboembolism [PE] and/or deep vein thromboembolism [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
The Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic Venous Thromboembolism (VTE) (by Type)	VTE (pulmonary thromboembolism [PE] and/or deep vein thromboembolism [DVT]) was adjudicated blindly by the Central Independent Adjudication Committee of Efficacy (CIACE).	From Day 1 to Day 90 (±7 days)
The Percentage of Participants With Perfusion Lung Scan Results Scored as Improved, no Change, or Worse	"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.	Baseline, Days 5-10 (the day when the medication [FPX or UFH] was finished /discontinued) (+/-1)
Total Perfusion Score at Baseline and Mean Change From Baseline at Days 5-10	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).	Baseline, Days 5-10 (the day when the medication [FPX or UFH] was finished /discontinued) (+/-1)
The Percentage of Participants With a Bleeding Event	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).	FPX or UFH treatment period (Days 5-10, on average)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General 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. doi: 10.1253/circj.cj-10-1036. Epub 2011 Apr 22.

Helpful Links

• 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 record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: September 3, 2009
• First Submitted That Met QC Criteria: September 21, 2009
• First Posted (Estimate): September 22, 2009

Study Record Updates

• Last Update Posted (Estimate): December 16, 2016
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Deep Vein Thrombosis; Fondaparinux sodium; contrast-enhanced MDCT; Pulmonary thromboembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Calcium heparin; Fondaparinux; PENTA
• Other Study ID Numbers: 106206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.

Study Data/Documents

1. Dataset Specification
   Information identifier: 106206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 106206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 106206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register