Biliary Tract Surgical Procedures, Colectomy, Esophagectomy, Gastrectomy, Pancreaticoduodenectomy
Conditions
Keywords
tranexamic acid, major abdominal surgery, blood loss
Brief summary
Tranexamic acid has been shown to reduce postoperative blood losses and transfusion requirements in various types of major surgery (orthopedic surgery, spine surgery, cardiopulmonary bypass, liver resections, and gynecological cancers).The current trial is being conducted to compare the efficacy of tranexamic acid plus standard of care versus standard of care in reduction of blood loss in patients undergoing major abdominal surgeries.
Interventions
DRUGTranexamic acid + 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patient undergoing major abdominal surgery (Biliary strictures, Pancreatico-duodenectomy, Esophagectomy, Total proctocolectomy, Hemicolectomy, Gastrectomy, Other major abdominal surgeries with similar expected blood loss)
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) * Patients with documented DVT or PE at screening or in past three months. * 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 |
|---|---|---|
| Post-operative Blood Loss | Post-operation, Day 1, Day 2 up to drain removal | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Blood Loss | Baseline through Day 2 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. |
| Total Blood Loss as Assessed by the Gross' Formula | Baseline through Day 2 post-surgery | Gross' formula for estimating total blood loss: Estimated blood volume multiplied by (\*) \[(hematocrit initial minus hematocrit final) divided by hematocrit average\]; 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. |
| Hemoglobin Levels | End of surgery, Day 1, Day 2, Day 4 and Day 7/End of treatment (EoT) post-surgery | — |
| Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery | Day 7 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. |
| Percentage 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 hematocrit 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). | 49 |
| Standard of Care Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss. | 45 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 3 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Tranexamic Acid Plus Standard of Care | Standard of Care | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 24 Participants | 16 Participants | 40 Participants |
| Age, Customized 45 to 64 years | 21 Participants | 22 Participants | 43 Participants |
| Age, Customized Greater than or equal to 65 years | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 33 Participants | 29 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 49 | 14 / 45 |
| serious Total, serious adverse events | 9 / 49 | 7 / 45 |
Outcome results
Primary
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: Post-operation, Day 1, Day 2 up to drain removal
Population: Full Analysis Set (FAS) population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Post-operative Blood Loss | 394.3 milliliter (mL) | Standard Deviation 366.36 |
| Standard of Care | Post-operative Blood Loss | 494.3 milliliter (mL) | Standard Deviation 503.94 |
Comparison: The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.p-value: 0.4695% CI: [-371.4, 171.5]t-test, 2 sided
Secondary
Hemoglobin Levels
Time frame: End of surgery, Day 1, Day 2, Day 4 and Day 7/End of treatment (EoT) post-surgery
Population: FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Hemoglobin Levels | Day 1 | 11.3 Gram/Deciliter (g/dL) | Standard Deviation 1.44 |
| Tranexamic Acid Plus Standard of Care | Hemoglobin Levels | Day 4 | 10.8 Gram/Deciliter (g/dL) | Standard Deviation 1.67 |
| Tranexamic Acid Plus Standard of Care | Hemoglobin Levels | Day 2 | 10.4 Gram/Deciliter (g/dL) | Standard Deviation 1.7 |
| Tranexamic Acid Plus Standard of Care | Hemoglobin Levels | Day 7/EoT | 11.0 Gram/Deciliter (g/dL) | Standard Deviation 1.38 |
| Tranexamic Acid Plus Standard of Care | Hemoglobin Levels | End of surgery | 11.6 Gram/Deciliter (g/dL) | Standard Deviation 2.16 |
| Standard of Care | Hemoglobin Levels | Day 7/EoT | 11.1 Gram/Deciliter (g/dL) | Standard Deviation 1.6 |
| Standard of Care | Hemoglobin Levels | End of surgery | 12.1 Gram/Deciliter (g/dL) | Standard Deviation 1.3 |
| Standard of Care | Hemoglobin Levels | Day 1 | 11.6 Gram/Deciliter (g/dL) | Standard Deviation 1.41 |
| Standard of Care | Hemoglobin Levels | Day 2 | 11.0 Gram/Deciliter (g/dL) | Standard Deviation 1.41 |
| Standard of Care | Hemoglobin Levels | Day 4 | 10.9 Gram/Deciliter (g/dL) | Standard Deviation 1.39 |
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 population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Intra-operative Blood Loss | 599.2 mL | Standard Deviation 419.58 |
| Standard of Care | Intra-operative Blood Loss | 682.8 mL | Standard Deviation 555.52 |
Comparison: The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.p-value: 0.57995% CI: [-386.5, 219.3]t-test, 2 sided
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 7 post-surgery
Population: FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Plus Standard of Care | Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery | 0 Participants |
| Standard of Care | Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery | 0 Participants |
Secondary
Percentage 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 hematocrit value of 24 percent.
Time frame: Up to Day 7 post-surgery
Population: FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Plus Standard of Care | Percentage of Participants Receiving Transfusions | 21.7 Percentage of participants |
| Standard of Care | Percentage of Participants Receiving Transfusions | 14.3 Percentage of participants |
Comparison: Fisher's exact test was used at 5% level of significance.p-value: 0.701Fisher Exact
Secondary
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 2 post-surgery
Population: FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Total Blood Loss | 993.6 mL | Standard Deviation 703.63 |
| Standard of Care | Total Blood Loss | 1177.1 mL | Standard Deviation 879.94 |
Comparison: The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.p-value: 0.45295% CI: [-672.6, 305.5]t-test, 2 sided
Secondary
Total Blood Loss as Assessed by the Gross' Formula
Gross' formula for estimating total blood loss: Estimated blood volume multiplied by (\*) \[(hematocrit initial minus hematocrit final) divided by hematocrit average\]; where estimated blood volume equals body weight in kilograms (kg) \*70 mL/kg.
Time frame: Baseline through Day 2 post-surgery
Population: FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Plus Standard of Care | Total Blood Loss as Assessed by the Gross' Formula | 17.8 mL | Standard Deviation 451.24 |
| Standard of Care | Total Blood Loss as Assessed by the Gross' Formula | 435.5 mL | Standard Deviation 558.74 |
Comparison: The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.p-value: 0.0195% CI: [-729.4, -106.1]t-test, 2 sided