Total Hip Replacement Study Of GSK576428 (Fondaparinux Sodium)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00320398
• Collaborator: (none)
• Enrollment: 114
• Location: 1
• Actual Duration (Months): 5.6
• Patients Per Site Per Month: 20.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Thrombosis, Venous	Drug: Fondaparinux	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Primary Purpose: Prevention
• Official Title: Clinical Evaluation of GSK576428 (Fondaparinux Sodium) in Prevention of Venous Thromboembolism After Elective Total Hip Replacement Surgery
• Actual Study Start Date: Jan 30, 2006
• Actual Primary Completion Date: Jul 18, 2006
• Actual Study Completion Date: Jul 18, 2006

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Venous Thromboembolism (VTE) During Efficacy Period [Up to Day 17]

   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).

2. Percentage of Participants With Major Bleeding [Up to Day 17]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Minor Bleeding [Up to Day 17]

   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.

2. Percentage of Participants With All Deep Vein Thrombosis (DVT) [Up to Day 17]

   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.

3. Percentage of Participants With Proximal DVT [Up to Day 17]

   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.

4. Percentage of Participants With Distal Only DVT [Up to Day 17]

   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.

5. Percentage of Participants With Symptomatic DVT During Main Efficacy Period [Up to Day 17]

   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.

6. Percentage of Participants With Pulmonary Embolism During Efficacy Period [Up to Day 17]

   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.

7. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths [From first injection of study drug (Day 3) to up to 2 calendar days after last injection (Treatment period), up to Day 17.]

   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.

8. Number of Transfused Participants [Up to Day 17.]

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

9. Volume of Transfusion [Up to Day 17]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00320398
• Other Study ID Numbers: AR3106333
• First Posted: May 3, 2006
• Last Update Posted: Sep 4, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Fondaparinux; Hip Replacement Arthroplasty; VTE; THR; MOSLL; pentasaccharide; Xa factor
• Additional relevant MeSH terms: Thrombosis; Venous Thrombosis; PENTA; Fondaparinux

Study Results

Participant Flow

Recruitment Details	A total of 115 participants who had undergone total Hip replacement surgery were randomized to the study. The study was conducted from 30 January 2006 to 18 July 2006 at eight centers in Japan. A total of 114 and 94 participants were included in Safety and Full analysis set population respectively.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 milligram (mg) administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Period Title: Overall Study
STARTED	58	56
COMPLETED	56	52
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg	Total
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Total of all reporting groups
Overall Participants	58	56	114
Age, Customized (Count of Participants)
>=20 years	58 100%	56 100%	114 100%
Sex: Female, Male (Count of Participants)
Female	51 87.9%	51 91.1%	102 89.5%
Male	7 12.1%	5 8.9%	12 10.5%
Region of Enrollment (Count of Participants)
Japan	58 100%	56 100%	114 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Venous Thromboembolism (VTE) During Efficacy Period
Description	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	48	46
Number (95% Confidence Interval) [percentage of participants]	8.3 14.3%	2.2 3.9%

2. Primary Outcome

Title	Percentage of Participants With Major Bleeding
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Minor Bleeding
Description	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

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Number (95% Confidence Interval) [percentage of participants]	1.7 2.9%	3.6 6.4%

4. Secondary Outcome

Title	Percentage of Participants With All Deep Vein Thrombosis (DVT)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	48	46
Number [percentage of participants]	8.3 14.3%	2.2 3.9%

5. Secondary Outcome

Title	Percentage of Participants With Proximal DVT
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	53	52
Number [percentage of participants]	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Distal Only DVT
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	48	46
Number [percentage participants]	4 6.9%	1 1.8%

7. Secondary Outcome

Title	Percentage of Participants With Symptomatic DVT During Main Efficacy Period
Description	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

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Number [percentage of participants]	0 0%	0 0%

8. Secondary Outcome

Title	Percentage of Participants With Pulmonary Embolism During Efficacy Period
Description	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

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Number [percentage of participants]	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths
Description	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.

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Deaths	0 0%	0 0%
Any SAE	0 0%	0 0%
Any AE	49 84.5%	45 80.4%

10. Secondary Outcome

Title	Number of Transfused Participants
Description	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.

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Number [participants]	5 8.6%	2 3.6%

11. Secondary Outcome

Title	Volume of Transfusion
Description	The total volume of transfusion (RBCs or WB) received by the participant was reported.
Time Frame	Up to Day 17

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Fondaparinux 1.5 mg	Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received fondaparinux at 1.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).	Eligible participants in this arm received fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
Measure Participants	58	56
Mean (Standard Deviation) [mL]	400.0 (0.0)	600.0 (282.8)

Adverse Events

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.
Adverse Event Reporting Description	Safety population was used.
Arm/Group Title	Fondaparinux 1.5 mg		Fondaparinux 2.5 mg
Arm/Group Description	Eligible participants in this arm received Fondaparinux at 1.5 milligram (mg) administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).		Eligible participants in this arm received Fondaparinux at 2.5 mg, administered as a subcutaneous injection once daily for 10 to 14 days (between Day 2 and Day 11- 15), (where Day 1 was the day of surgery). The first injection of the study drug was given 24 + or - 2 hours after the surgical closure. From Day 3 onwards the injection of the study drug was given at about the same time every day as far as possible (but more than 12 hours after the first dose on Day 2).
All Cause Mortality
	Fondaparinux 1.5 mg		Fondaparinux 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/56 (0%)
Serious Adverse Events
	Fondaparinux 1.5 mg		Fondaparinux 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Fondaparinux 1.5 mg		Fondaparinux 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/58 (84.5%)		45/56 (80.4%)
Gastrointestinal disorders
Constipation	5/58 (8.6%)		10/56 (17.9%)
Haemorrhoids	1/58 (1.7%)		2/56 (3.6%)
Abdominal pain upper	5/58 (8.6%)		1/56 (1.8%)
Diarrhoea	3/58 (5.2%)		0/56 (0%)
Nausea	3/58 (5.2%)		0/56 (0%)
General disorders
Pyrexia	3/58 (5.2%)		0/56 (0%)
Hepatobiliary disorders
Hepatic function abnormal	2/58 (3.4%)		2/56 (3.6%)
Investigations
Platelet count increased	7/58 (12.1%)		5/56 (8.9%)
Gamma glutamyl transferase increased	1/58 (1.7%)		3/56 (5.4%)
Blood alkaline phosphatase increased	2/58 (3.4%)		2/56 (3.6%)
Musculoskeletal and connective tissue disorders
Myalgia	12/58 (20.7%)		14/56 (25%)
Pain in extremity	1/58 (1.7%)		4/56 (7.1%)
Back pain	6/58 (10.3%)		0/56 (0%)
Nervous system disorders
Headache	5/58 (8.6%)		2/56 (3.6%)
Dizziness	3/58 (5.2%)		2/56 (3.6%)
Psychiatric disorders
Insomnia	9/58 (15.5%)		13/56 (23.2%)
Skin and subcutaneous tissue disorders
Pruritus	3/58 (5.2%)		9/56 (16.1%)
Dermatitis contact	2/58 (3.4%)		2/56 (3.6%)
Erythema	2/58 (3.4%)		2/56 (3.6%)
Rash	1/58 (1.7%)		2/56 (3.6%)
Urticaria	0/58 (0%)		2/56 (3.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.