Hematologic Neoplasms
Conditions
Brief summary
It is hypothesized that a strategy using prophylactic oral Tranexamic Acid (TXA) with therapeutic platelet transfusions is safe and effective compared to prophylactic platelet transfusions in patients undergoing an autologous hematopoietic stem cell transplantation (who are at risk for bleeding).
Detailed description
In Canada, over 1,500 autologous hematopoietic stem cell transplantations (ASCT) are performed annually for hematologic malignancies. It is currently standard practice to provide a prophylactic transfusion of platelets to prevent bleeding when the daily measured platelet count is less than 10 x 109/L. A patient may require up to six adult platelet doses during the post-transplant period. However, the true benefit of prophylactic platelet transfusions in the ASCT setting is unclear and has been called into question by several recent studies. Prophylactic platelet transfusions may not only be unnecessary, they may be detrimental to the patient. Among blood products, platelet transfusions are associated with the highest risk of both infectious and non-infectious complications: this would include bacterial infections and allergic /febrile reactions. Moreover, the potential overuse of platelet products places a significant burden on a scarce health care resource that is provided through volunteer donations. An alternative strategy to prevent bleeding and reduce the need for platelet transfusions involves administering Tranexamic Acid, an oral antifibrinolytic agent to stabilize blood clots and reduce bleeding. Tranexamic Acid is safe and effective in many clinical scenarios, and may be a reasonable alternative for prophylactic platelet transfusions. In the setting of ASCT, Tranexamic Acid may reduce bleeding and further enhance a strategy of therapeutic platelet transfusions where platelets are administered only in the event of active bleeding symptoms. The effect of prophylactic platelet transfusions and Tranexamic Acid on clinical, quality of life and economic outcomes in patients receiving ASCT is unknown. The primary aim of this research program is to perform a randomized controlled trial to determine whether a strategy of prophylactic Tranexamic Acid (with therapeutic platelet transfusions) is safe and effective compared to prophylactic platelet transfusions in patients undergoing ASCT. Before conducting a larger trial, the investigators first propose a pilot randomized controlled trial to determine the feasibility of such a study.
Interventions
DRUGTranexamic Acid
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1\. Patients are aged 18 years old or older and undergoing an autologous HSCT (hematopoietic stem cell transplantation) for any hematologic malignancy.
Exclusion criteria
1. A previous WHO grade 3 or 4 bleeding event 2. A WHO grade 2 bleeding event within the past year 3. A previous or current unprovoked thrombotic event defined as a pulmonary embolism, deep vein thrombosis, cerebral thrombosis 4. Current or previous (within 2 weeks) urinary tract bleeding 5. An inherited hemostatic or thrombotic disorder 6. Coagulopathy defined as a prothrombin time or activated partial thromboplastin time \>1.5 times the upper limit of normal or fibrinogen less than 2 g/L 7. A requirement for therapeutic anticoagulant or antiplatelet drugs 8. Previously documented history of refractoriness to platelet transfusion secondary to HLA (Human Leukocyte Antigen) antibodies 9. Significant renal impairment (creatinine \>1.5 times the upper limit of normal) 10. Pregnant or breast-feeding 11. Unwilling or unable to provide informed consent 12. Participant has ever had a pulmonary embolism, deep vein thrombosis, cerebral thrombosis or has active angina 13. Participant has known history of subarachnoid hemorrhage 14. Participant has acquired disturbances to his/her colour vision 15. Participant has known sensitivity or allergy to Tranexamic Acid or any of its ingredients 16. The current use of oral contraceptive pill (Birth Control Pill), hormonal contraceptives or hormone replacement therapy .
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Enrolment, as measured by the number of patients screened per month at each site | monthly, up to 23 months |
| Number of off-protocol platelet transfusions, with a target of < 10% off-protocol transfusions in each treatment arm | monthly, up to 23 months |
| Total number of platelet transfusions/group, with a target of 25% reduction in the tranexamic acid arm | monthly, up to 23 months |
| Adherence to tranexamic acid use, defined as excellent (greater than or equal to 90% use), acceptable (75-90% use), poor (< 75% use) | monthly, up to 23 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of platelet and/or red cell transfusions | daily, up to one month | — |
| Time to platelet recovery | daily, up to one month | — |
| Number of days with platelet count < 10 x 10^9/L | daily, up to one month | — |
| LOS (Length of hospital stay) | Length of stay will be measured as the number of days elapsed between hospital admission and hospital discharge dates up to 1 month | LOS=discharge date - admission date |
| WHO (World Health Organization) Bleeding events of Grade 2 or higher | daily, up to one month | — |
| Bearman Toxicity Score | Day 30 | Validated scoring system to assess toxicity during stem cell transplantation |
| Infections at Day 30 | Day 30 | — |
| Quality of Life measurements, as determined by a battery of QoL instruments | daily, up to one month | — |
| Adverse transfusion reactions | daily, up to one month | Number and type of reactions will be recorded. |
| Time from randomization to bleeding of WHO bleeding events Grade 2 or higher | daily, up to one month | — |
| Number of days with bleeding of WHO bleeding events Grade 2 or higher | daily, up to one month | — |
| Bleeding Severity Measurement Scale for bleeding events Grade 2 or higher | daily, up to one month | — |
Countries
Canada
Outcome results
None listed