Femoral Fractures
Conditions
Keywords
Tranexamic Acid, Blood Loss, Long Bone Fracture Surgery
Brief summary
Tranexamic acid has been shown to reduce postoperative blood losses and transfusion requirements in a number of types of surgery. Most trials in orthopedic surgery have been conducted in arthroplasty, hip fracture and spine surgeries. This study would aim to see the effect of tranexamic acid in reduction of blood loss and transfusions for long bone fracture surgery, primarily fracture shaft of femur.
Interventions
DRUGTranexamic Acid plus standard of care
Tranexamic acid given slowly intravenously (15 mg/kg body weight) 15 minutes before surgery followed by a second dose at three hour interval from first dose and third dose at three hour interval from the second + Standard of care (Standard of care includes the routine surgical and anesthetic techniques being utilized to control blood loss)
PROCEDUREStandard of care
Standard of care includes the routine surgical and anesthetic techniques being utilized to control blood loss
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Patient undergoing surgery for fracture shaft of femur
Exclusion criteria
* Patients with a platelet count less than 100, 000/mm3 or history of thrombocytopenia * Patients with known coagulopathy * Patients with anemia (hemoglobin levels less than 8 mg/dl or hematocrit \<24%) * Patients with documented DVT or PE at screening or in past three months * Patients having known hypersensitivity to tranexamic acid or any other constituent of the product * Patients with any associated major illness (e.g., severe cardiac or respiratory disease) * Anticoagulants (other than LMWH or heparin in prophylactic doses to prevent deep vein thrombosis), direct thrombin inhibitors or thrombolytic therapy administered or completed within last week
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Blood Loss | Baseline through Day 7 post-surgery | Total blood loss was defined as the sum of intra-operative and post-operative blood loss. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative Blood Loss | 1, 4, 8 and 24 hours post-surgery | Post-operative blood loss was defined as the sum of the drainage volumes measured over post-operative days 1, 2, and at drain removal. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed. |
| Total Blood Loss Assessed by Gross' Formula | Day 7 post-surgery | Gross's formula for estimating total blood loss: Estimated blood volume\*\[(Hematocrit initial - Hematocrit final)/ Hematocrit average\]; where estimated blood volume equals body weight in kilograms (kg) \*70 mL/kg. |
| Intra-operative Blood Loss | Day 1 (End of surgery) | Intra-operative blood loss was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed. |
| Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Baseline through end of surgery, 1 hr post-surgery, and mornings of Day 1, Day 2, Day 4, Day 7 or ET post-surgery | — |
| Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery | Day 5 post-surgery | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling and warmth. |
| Number of Participants Receiving Transfusions | Up to day 7 post-surgery | A uniform transfusion protocol was maintained for all participants in the study. Transfusion to be triggered at 8.0 milligram/deciliter (mg/dl) hemoglobin or haematocrit value of 24 percent. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tranexamic Acid Plus Standard of Care Tranexamic acid given slowly intravenously (IV) (15 milligram (mg) / kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss). | 41 |
| Standard of Care Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss. | 40 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 7 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Randomized, but not treated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Tranexamic Acid Plus Standard of Care | Standard of Care | Total |
|---|---|---|---|
| Age Continuous | 33.7 Years STANDARD_DEVIATION 12.6 | 36.6 Years STANDARD_DEVIATION 17 | 35.1 Years STANDARD_DEVIATION 14.9 |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 36 Participants | 33 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 41 | 26 / 40 |
| serious Total, serious adverse events | 4 / 41 | 1 / 40 |
Outcome results
Primary
Total Blood Loss
Total blood loss was defined as the sum of intra-operative and post-operative blood loss. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.
Time frame: Baseline through Day 7 post-surgery
Population: Full analysis set (FAS) included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Total Blood Loss | 370.7 Milliliters (mL) | Standard Deviation 180.7 |
| Standard of Care | Total Blood Loss | 426.2 Milliliters (mL) | Standard Deviation 323.8 |
Comparison: The mean difference with associated standard error (SE), and corresponding 95% confidence interval (CI) for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.34895% CI: [-172.7, 61.7]t-test, 2 sided
Secondary
Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery
Time frame: Baseline through end of surgery, 1 hr post-surgery, and mornings of Day 1, Day 2, Day 4, Day 7 or ET post-surgery
Population: FAS included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at end of surgery | -1.7 gram/deciliter (g/dl) | Standard Deviation 1.2 |
| Tranexamic Acid Plus Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at day 1 post-surgery | -2.1 gram/deciliter (g/dl) | Standard Deviation 1.1 |
| Tranexamic Acid Plus Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Baseline | 13.1 gram/deciliter (g/dl) | Standard Deviation 1.5 |
| Tranexamic Acid Plus Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at day 2 post-surgery | -2.1 gram/deciliter (g/dl) | Standard Deviation 1.2 |
| Tranexamic Acid Plus Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at 1 hour post-surgery | -1.8 gram/deciliter (g/dl) | Standard Deviation 1.1 |
| Tranexamic Acid Plus Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at day 4 post-surgery or ET | -2.0 gram/deciliter (g/dl) | Standard Deviation 1.4 |
| Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at 1 hour post-surgery | -1.9 gram/deciliter (g/dl) | Standard Deviation 1.3 |
| Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Baseline | 12.9 gram/deciliter (g/dl) | Standard Deviation 2.1 |
| Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at end of surgery | -2.0 gram/deciliter (g/dl) | Standard Deviation 1.5 |
| Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at day 4 post-surgery or ET | -2.1 gram/deciliter (g/dl) | Standard Deviation 1.5 |
| Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at day 1 post-surgery | -2.2 gram/deciliter (g/dl) | Standard Deviation 1.4 |
| Standard of Care | Change From Baseline in Hemoglobin Levels at End of Surgery, 1 hr Post-surgery, and Mornings of Day 1, Day 2, Day 4, Day 7 or Early Termination (ET) Post-surgery | Change at day 2 post-surgery | -2.3 gram/deciliter (g/dl) | Standard Deviation 1.4 |
Comparison: For change at end of surgery, a Mixed Model Repeated Measures (MMRM) approach was used to relate the dependent (outcome) variable and independent (treatment, time point, and treatment-by-time point interaction as factors and baseline value as co-variate) variables taking into account the within-participant correlation arising from the repeated measurements.p-value: 0.20895% CI: [-0.21, 0.96]Mixed Models Analysis
Comparison: For change at 1 hour post-surgery, a MMRM approach was used to relate the dependent (outcome) variable and independent (treatment, time point, and treatment-by-time point interaction as factors and baseline value as co-variate) variables taking into account the within-participant correlation arising from the repeated measurements.p-value: 0.68295% CI: [-0.4, 0.61]Mixed Models Analysis
Comparison: For change at day 1 post-surgery, a MMRM approach was used to relate the dependent (outcome) variable and independent (treatment, time point, and treatment-by-time point interaction as factors and baseline value as co-variate) variables taking into account the within-participant correlation arising from the repeated measurements.p-value: 0.56995% CI: [-0.35, 0.63]Mixed Models Analysis
Comparison: For change at day 2 post-surgery, a MMRM approach was used to relate the dependent (outcome) variable and independent (treatment, time point, and treatment-by-time point interaction as factors and baseline value as co-variate) variables taking into account the within-participant correlation arising from the repeated measurements.p-value: 0.41395% CI: [-0.29, 0.7]Mixed Models Analysis
Comparison: For change at day 4/ET post-surgery, a MMRM approach was used to relate the dependent (outcome) variable and independent (treatment, time point, and treatment-by-time point interaction as factors and baseline value as co-variate) variables taking into account the within-participant correlation arising from the repeated measurements.p-value: 0.68695% CI: [-0.44, 0.66]Mixed Models Analysis
Secondary
Intra-operative Blood Loss
Intra-operative blood loss was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.
Time frame: Day 1 (End of surgery)
Population: FAS included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Intra-operative Blood Loss | 316.2 mL | Standard Deviation 129.8 |
| Standard of Care | Intra-operative Blood Loss | 292.2 mL | Standard Deviation 161.6 |
Comparison: The mean difference with associated SE and corresponding 95% CI for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.46695% CI: [-41.3, 89.3]t-test, 2 sided
Secondary
Number of Participants Receiving Transfusions
A uniform transfusion protocol was maintained for all participants in the study. Transfusion to be triggered at 8.0 milligram/deciliter (mg/dl) hemoglobin or haematocrit value of 24 percent.
Time frame: Up to day 7 post-surgery
Population: FAS included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Plus Standard of Care | Number of Participants Receiving Transfusions | 5 Participants |
| Standard of Care | Number of Participants Receiving Transfusions | 6 Participants |
Comparison: Chi-square test was used at 5% level of significance.p-value: 0.714Chi-squared
Secondary
Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery
DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling and warmth.
Time frame: Day 5 post-surgery
Population: FAS included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Plus Standard of Care | Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery | 3 Participants |
| Standard of Care | Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery | 0 Participants |
Comparison: Fisher's exact test at 5% level of significance was used as the event rate was low and the expected count for any cell in the (unstratified) 2\*2 contingency table was less than 5.p-value: 0.241Fisher Exact
Secondary
Post-operative Blood Loss
Post-operative blood loss was defined as the sum of the drainage volumes measured over post-operative days 1, 2, and at drain removal. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.
Time frame: 1, 4, 8 and 24 hours post-surgery
Population: FAS included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Post-operative Blood Loss | 1 hour | 0.2 mL | Standard Deviation 1.6 |
| Tranexamic Acid Plus Standard of Care | Post-operative Blood Loss | 4 hours | 0.6 mL | Standard Deviation 3.2 |
| Tranexamic Acid Plus Standard of Care | Post-operative Blood Loss | 8 hours | 0.7 mL | Standard Deviation 3.5 |
| Tranexamic Acid Plus Standard of Care | Post-operative Blood Loss | 24 hours | 27.4 mL | Standard Deviation 67.5 |
| Standard of Care | Post-operative Blood Loss | 24 hours | 50.1 mL | Standard Deviation 68.9 |
| Standard of Care | Post-operative Blood Loss | 1 hour | 9.5 mL | Standard Deviation 35.6 |
| Standard of Care | Post-operative Blood Loss | 8 hours | 7.5 mL | Standard Deviation 26.7 |
| Standard of Care | Post-operative Blood Loss | 4 hours | 7.4 mL | Standard Deviation 20.5 |
Comparison: For 1 hour post-surgery, the mean difference with associated SE and corresponding 95% CI for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.10995% CI: [-20.7, 2.2]t-test, 2 sided
Comparison: For 4 hour post-surgery, the mean difference with associated SE, and corresponding 95% CI for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.04595% CI: [-13.4, -0.1]t-test, 2 sided
Comparison: For 8 hour post-surgery, the mean difference with associated SE, and corresponding 95% CI for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.11995% CI: [-15.4, 1.8]t-test, 2 sided
Comparison: For 24 hour post-surgery, the mean difference with associated SE, and corresponding 95% CI for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.13995% CI: [-52.9, 7.5]t-test, 2 sided
Secondary
Total Blood Loss Assessed by Gross' Formula
Gross's formula for estimating total blood loss: Estimated blood volume\*\[(Hematocrit initial - Hematocrit final)/ Hematocrit average\]; where estimated blood volume equals body weight in kilograms (kg) \*70 mL/kg.
Time frame: Day 7 post-surgery
Population: FAS included all participants who were randomized to study treatment and received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Total Blood Loss Assessed by Gross' Formula | 823.2 mL | Standard Deviation 676.6 |
| Standard of Care | Total Blood Loss Assessed by Gross' Formula | 798.0 mL | Standard Deviation 490.2 |
Comparison: The mean difference with associated SE, and corresponding 95% CI for the comparisons of tranexamic acid plus standard of care against Standard of care was presented along with the p-value for the test. Two-sample t-test was performed at 5% level of significance.p-value: 0.84995% CI: [-238.2, 288.6]t-test, 2 sided