Total Hip Replacement Study Of GSK576428 (Fondaparinux Sodium)

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.

Time frame: Up to Day 17

Population: The safety population consisted of all participants who received at least one dose of randomized study drug.

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).

Time frame: Up to Day 17

Population: The Full Analysis Set (FAS) population consisted of all participants who were randomized to either treatment with the exception of: those who did not receive study drug at all; and those with no valid post-randomization efficacy data (e.g., no evaluable venogram).

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.

Time frame: From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17.

Population: Safety population.

The number of participants who received RBCs or WB after the total hip replacement surgery within 48 hours of bleed were reported.

Time frame: Up to Day 17.

Population: Safety population.

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.

Time frame: Up to Day 17

Population: Efficacy Evaluable Patients (EEP) included subpopulation of safety participants judged to be evaluable for all DVT, proximal DVT or distal only DVT by site of occurrence (total/ side of operation/ opposite side of operation/ both sides). Only those participants with data available at the indicated time points were analyzed.

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.

Time frame: Up to Day 17

Population: EEP population. Only those participants with data available at the indicated time points were analyzed.

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.

Time frame: Up to Day 17

Population: Safety population.

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.

Time frame: Up to Day 17

Population: EEP population. Only those participants with data available at the indicated time points were analyzed.

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.

Time frame: Up to Day 17

Population: Safety population.

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.

Time frame: Up to Day 17

Population: Safety population.

The total volume of transfusion (RBCs or WB) received by the participant was reported.

Time frame: Up to Day 17

Population: Safety population.