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

Embolism, Pulmonary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00981409
• Other study ID #: 106206
• Status: Completed
• Phase: Phase 3
• First received: September 3, 2009
• Last updated: July 7, 2011
• Start date: July 2007
• Est. completion date: December 2008

Study information

• Verified date: July 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Acute Pulmonary Thromboembolism
• Embolism, Pulmonary
• Pulmonary Embolism
• Thromboembolism

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	Fukuoka
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Niigata
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
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	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	Yes