Hip Fracture Study of GSK576428 (Fondaparinux Sodium)

Study Overview
=================
Brief Summary
-----------------
This study is requested by PMDA to confirm the efficacy and the safety for HFS.

Official Title
-----------------
Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in Prevention of Venous Thromboembolism After Hip Fracture Surgery

Conditions
-----------------
Thromboembolism

Intervention / Treatment
-----------------
* Drug: Fondaparinux


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing hip fracture surgery within 10 days following the time of fracture of the hip (proximal femur) (or following the time of fracture estimated from trauma). Exclusion Criteria: Active, clinically significant bleeding (excluding drainage).

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Fondaparinux|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Major Bleeding During Treatment Period | Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of venous thromboembolic events (VTE) included, but were not limited to lower extremity deep vein thrombosis (DVT): erythema, warmth, pain, swelling, tenderness and pulmonary embolism (PE): pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the Central Independent Adjudication Committee of Efficacy (CIACE). | From the first study drug injection up to Day 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of PE During Treatment Period | Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first. | Up to Day 17 | 
| Rate of DVT During Treatment Period | Rate (%) was defined as number of events divided by the number of patients evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first. | Up to Day 17 | 
| Rate of Proximal DVT During Treatment Period | Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first. | Up to Day 17 | 
| Rate of Distal Only DVT During Treatment Period | Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first. | Up to Day 17 | 
| Number of Participants With Major Bleeding During Treatment Period | Major bleeding events were defined as clinically unusual bleeding meeting any of the following criteria: fatal bleeding, bleeding including retroperitoneal and intracranial bleeding or bleeding into a critical organ (eye, adrenal gland, pericardium, spine), reoperation due to bleeding/hematoma at the operative site, bleeding leading to a hemoglobin (Hb) fall >=2 grams per deciliter (g/dL, 1.6 millimoles per liter [mmol/L]) within 48 hour of the bleed, bleeding that required a transfusion of red blood cell or whole blood derived from >=900 millilters (mL) of whole blood within 48 hours of the bleed (excluding the autologous transfusion except for the treatment of bleeding adverse event (AE) and bleeding leading to the bleeding index (BI) >=2. Major bleeding events were adjudicated by the Central Independent Adjudication Committee of Safety (CIACS). | From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17) | 
| Number of Participants With Minor Bleeding and Any Bleeding (Major and/or Minor Bleeding) | Minor bleeding and any bleeding (major and/or minor bleeding) events were adjudicated by the CIACS. Minor bleeding was defined as clinically overt bleeding not meeting the criteria for major bleeding and considered more than expected in the clinical context. Any bleeding (major and/or minor bleeding) could be recorded may be major and/or minor. | From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17) | 
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death | An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. | From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17) | 
| Number of Transfused Participants | Blood product transfusions consisted of packed red blood cells or fresh frozen plasma or both. This was done between Day 2 and 2 calendar days after the last injection. | From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17) | 
| Summary of Units Transfused | Blood product transfusions consisted of packed red blood cells or fresh frozen plasma or both. This was done between Day 2 and 2 calendar days after the last injection. | From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17) | 
| Rate of Symptomatic DVT | Rate (%) was defined as number of events divided by the number of participants evaluated multiplied by 100. Signs and symptoms suggestive of VTE included, but were not limited to lower extremity DVT: erythema, warmth, pain, swelling, tenderness. Intended treatment period started 24±2 hours after surgical closure. Venogram was obtained not later than 2 calendar days after the last study drug administration (between Day 11 and 17). These events were adjudicated by the CIACE. It was evaluated from the first study drug injection up to Day 17 or to first venogram, whichever occurred first. | Up to Day 17 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Xa factor, VTE, MOSLL, pentasaccharide