Trial Outcomes & Findings for Hip Fracture Study of GSK576428 (Fondaparinux Sodium) (NCT NCT00320424)
NCT ID: NCT00320424
Last Updated: 2018-09-04
Results Overview
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).
COMPLETED
PHASE3
48 participants
From the first study drug injection up to Day 17
2018-09-04
Participant Flow
Total of 48 participants undergoing major orthopedic surgery of the lower limb such as hip fracture surgery, knee replacement surgery and hip replacement surgery were enrolled from 16 February 2006 to 26 October 2006 at 9 centers in Japan. The safety population consisted of 48 participants and full analysis set consisted of 37 participants.
Participant milestones
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
Participants received fondaparinux sodium 2.5 milligrams (mg) by subcutaneous (s.c.) injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Overall Study
STARTED
|
48
|
|
Overall Study
COMPLETED
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42
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
Participants received fondaparinux sodium 2.5 milligrams (mg) by subcutaneous (s.c.) injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Overall Study
Adverse Event
|
3
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Overall Study
Other
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3
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Baseline Characteristics
Hip Fracture Study of GSK576428 (Fondaparinux Sodium)
Baseline characteristics by cohort
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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Age, Continuous
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76.6 Years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
Sex: Female, Male
Female
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40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
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48 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the first study drug injection up to Day 17Population: Full analysis set used which consisted of all participants who were assigned to study drug with the exception of those who did not receive study drug at all and those with no valid efficacy data (example no evaluable venogram).
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).
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=37 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Rate of Major Bleeding During Treatment Period
|
21.6 % of normalized events per participant
Interval 9.8 to 38.2
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SECONDARY outcome
Timeframe: Up to Day 17Population: Safety population used which consisted of all participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Rate of PE During Treatment Period
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0 % of normalized events per participant
Interval 0.0 to 0.0
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SECONDARY outcome
Timeframe: Up to Day 17Population: Efficacy evaluable participants used consisted of a subpopulation of safety population who were judged to be evaluable for all DVT and proximal DVT or distal only DVT by the 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.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=37 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Rate of DVT During Treatment Period
|
21.6 % of normalized events per participant
|
SECONDARY outcome
Timeframe: Up to Day 17Population: Efficacy evaluable participants used. Only those participants with data available at the indicated time points were analyzed.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=38 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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Rate of Proximal DVT During Treatment Period
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2.6 % of normalized events per participant
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SECONDARY outcome
Timeframe: Up to Day 17Population: Efficacy evaluable participants used. Only those participants with data available at the indicated time points were analyzed.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=37 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Rate of Distal Only DVT During Treatment Period
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21.6 % of normalized events per participant
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SECONDARY outcome
Timeframe: From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)Population: Safety population used.
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).
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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Number of Participants With Major Bleeding During Treatment Period
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0 Participants
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SECONDARY outcome
Timeframe: From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)Population: Safety population used.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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Number of Participants With Minor Bleeding and Any Bleeding (Major and/or Minor Bleeding)
Minor Bleeding
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0 Participants
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Number of Participants With Minor Bleeding and Any Bleeding (Major and/or Minor Bleeding)
Any Bleeding
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0 Participants
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SECONDARY outcome
Timeframe: From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)Population: Safety population used.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death
Any AE
|
37 Participants
|
|
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death
Any SAE
|
2 Participants
|
|
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death
Death
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0 Participants
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SECONDARY outcome
Timeframe: From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)Population: Safety population used.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Number of Transfused Participants
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1 Participants
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SECONDARY outcome
Timeframe: From the first study drug injection up to 2 days after the last study drug injection (approximately up to Day 17)Population: Safety population used.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Summary of Units Transfused
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280 mL
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SECONDARY outcome
Timeframe: Up to Day 17Population: Safety population used.
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.
Outcome measures
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 Participants
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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Rate of Symptomatic DVT
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0 % of normalized events per participant
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Adverse Events
Fondaparinux Sodium 2.5 mg s.c.
Serious adverse events
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 participants at risk
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Gastrointestinal disorders
Ileus
|
2.1%
1/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
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Injury, poisoning and procedural complications
Femur fracture
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2.1%
1/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
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Other adverse events
| Measure |
Fondaparinux Sodium 2.5 mg s.c.
n=48 participants at risk
Participants received fondaparinux sodium 2.5 mg by s.c. injection for 14 days between Day 2 to Day 11-15. The first injection of the study drug was given 24 ± 2 hours after 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).
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|---|---|
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Gastrointestinal disorders
Constipation
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16.7%
8/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
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|
Psychiatric disorders
Insomnia
|
16.7%
8/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
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|
General disorders
Oedema peripheral
|
8.3%
4/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Injury, poisoning and procedural complications
Excoriation
|
8.3%
4/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
8.3%
4/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Psychiatric disorders
Restlessness
|
6.2%
3/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
General disorders
Pyrexia
|
6.2%
3/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Investigations
Blood alkaline phosphatase increased
|
6.2%
3/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Gastrointestinal disorders
Diarrhea
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Investigations
C reactive protein increased
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Investigations
Platelet count increased
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
2/48 • AE and SAE were reported throughout the study (from the first study drug injection up to 2 days after the last study drug injection [approximately up to Day 17]).
Safety population was used for reporting AE and SAE.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER