Total Hip Replacement Study Of GSK576428 (Fondaparinux Sodium)

Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in Prevention of Venous Thromboembolism After Elective Total Hip Replacement Surgery

This study is requested by PMDA to confirm the optimal dose for THR (total hip replacement).

Study Overview

• Status: Completed
• Conditions: Thrombosis, Venous
• Intervention / Treatment: Drug: Fondaparinux

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 3

Contacts and Locations

Study Locations

• • • 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:

• Patients undergoing either an elective primary THR (total hip replacement) surgery or a revision of a THR.

Exclusion Criteria:

• Active, clinically significant bleeding (excluding drainage).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Venous Thromboembolism (VTE) During Efficacy Period	The percentage of participants with VTE, who underwent elective total hip replacement surgery, detected by routine venography, during the treatment period were reported. The percentage VTE was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the Central Independent Adjudication Committee of Efficacy (CIACE).	Up to Day 17
Percentage of Participants With Major Bleeding	Major bleeding defined as any clinically unusual bleeding meeting 1 of following criteria; a)Fatal bleeding; b) Including retroperitoneal and intracranial bleeding, or bleeding into critical organ (eye, adrenal gland, pericardium, spine); c) Reoperation due to bleeding or hematoma at operative site; d)Bleeding leading to hemoglobin (Hb) fall > = 2 gram per deciliter (g/dL)(1.6 millimole per litre [mmol/L]) within 48 hour of the bleed; e)Bleeding that required transfusion of red blood cells (RBCs) or whole blood (WB) derived from >= 900 milliliter (mL) of WB within 48 hours of the bleed (excluding autologous transfusion except for treatment of bleeding adverse event); f) Bleeding leading to bleeding index (BI) >=2. The percentage was calculated by the number of events divided by the number of participants evaluated multiplied by 100. This was adjudicated by the CIACE.	Up to Day 17

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Minor Bleeding	Minor bleeding was defined as the clinically overt bleeding not meeting the criteria for major bleeding like: (Fatal bleed; Including retroperitoneal and intracranial bleeding, or bleed in critical organ [eye, adrenal gland, pericardium, spine]; c) Reoperation due to bleeding or hematoma at operative site; d) Bleeding leading to hemoglobin (Hb) fall > = 2 g/dL(1.6 mmol/L) within 48 hour of the bleed; e)Bleeding that required transfusion of RBCs or WB derived from >= 900 mL of WB within 48 hours of the bleed (excluding autologous transfusion except for treatment of bleeding adverse event); f) Bleeding leading to bleeding index (BI) >=2), and which were considered more than expected in the clinical context. The percentage was calculated by the number of events divided by the number of participants evaluated multiplied by 100. This was adjudicated by the CIACE.	Up to Day 17
Percentage of Participants With All Deep Vein Thrombosis (DVT)	The percentage of participants with All DVT were reported, where the analysis was done using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.	Up to Day 17
Percentage of Participants With Proximal DVT	The percentage of participants with DVT (proximal) were reported, by using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.	Up to Day 17
Percentage of Participants With Distal Only DVT	The percentage of participants with distal only DVT were reported, by using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.	Up to Day 17
Percentage of Participants With Symptomatic DVT During Main Efficacy Period	The percentage of participants with different symptoms of DVT (proximal) like pain or tenderness, swelling, warmth, redness or discoloration, and distention of surface veins, post the total hip replacement surgery were reported, where analysis was done using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.	Up to Day 17
Percentage of Participants With Pulmonary Embolism During Efficacy Period	The percentage of participants with pulmonary embolism (pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia ) were reported, by using a venogram. It was calculated by the number of events divided by the number of participants evaluated multiplied by 100. The Venogram was obtained post 2 calendar days after the administration of last study drug (between Day 11 and 17). Day 1 was the day of surgery and the participant was given study drug 24±2 hours after surgical closure. It was adjudicated by the CIACE.	Up to Day 17
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths	An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.	From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17.
Number of Transfused Participants	The number of participants who received RBCs or WB after the total hip replacement surgery within 48 hours of bleed were reported.	Up to Day 17.
Volume of Transfusion	The total volume of transfusion (RBCs or WB) received by the participant was reported.	Up to Day 17

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2006
• Primary Completion (Actual): July 18, 2006
• Study Completion (Actual): July 18, 2006

Study Registration Dates

• First Submitted: May 1, 2006
• First Submitted That Met QC Criteria: May 1, 2006
• First Posted (Estimate): May 3, 2006

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: THR; VTE; Fondaparinux; Hip Replacement Arthroplasty; MOSLL; pentasaccharide; Xa factor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Fondaparinux; PENTA
• Other Study ID Numbers: AR3106333

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No