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

Phase 3

Completed

• Conditions: Embolism, Pulmonary
• Interventions: Drug: Fondaparinux sodium; Drug: unfractionated heparin (UFH)

• Registration Number: NCT00981409
• Lead Sponsor: GlaxoSmithKline

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Study First Submitted: 2009-09-03
• Study First Submitted QC: 2009-09-21
• Study First Posted: 2009-09-22
• Results First Submitted: 2009-10-14
• Results First Submitted QC: 2009-11-06
• Results First Posted: 2009-12-10
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-04
• Last Update Posted: 2016-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fondaparinux	Fondaparinux sodium	-
unfractionated heparin	unfractionated heparin (UFH)	-

Primary Outcome Measures

Name	Time	Method
The Percentage of Participants With Recurrent or New Symptomatic Venous Thromboembolism (VTE)	From Day 1 to Day 90 (±7 days)	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

Name	Time	Method
The Percentage of Participants With a Bleeding Event	FPX or UFH treatment period (Days 5-10, on average)	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).
The Percentage of Participants With Recurrent or New Symptomatic/Asymptomatic Venous Thromboembolism (VTE) (by Type)	From Day 1 to Day 90 (±7 days)	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	Baseline, Days 5-10 (the day when the medication [FPX or UFH] was finished /discontinued) (+/-1)	"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	Baseline, Days 5-10 (the day when the medication [FPX or UFH] was finished /discontinued) (+/-1)	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).

Trial Locations

Locations (1)

GSK Investigational Site; 🇯🇵 Tokyo, Japan