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

Thrombosis, Venous Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00911157
• Other study ID #: 111436
• Status: Completed
• Phase: Phase 3
• First received: May 28, 2009
• Last updated: March 17, 2011
• Start date: June 2008
• Est. completion date: November 2009

Study information

• Verified date: March 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Deep Vein Thrombosis
• Thrombosis
• Thrombosis, Venous
• Venous Thrombosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Niigata
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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).	Yes