Platelet Transfusion Requirements in Hematopoietic Transplantation Pilot Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Platelet Transfusion Requirements in Hematopoietic Transplantation(PATH Pilot)

Conditions
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Hematologic Neoplasms

Intervention / Treatment
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* Drug: Tranexamic Acid


Participation Criteria
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Eligibility Criteria
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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: A previous WHO grade 3 or 4 bleeding event A WHO grade 2 bleeding event within the past year A previous or current unprovoked thrombotic event defined as a pulmonary embolism, deep vein thrombosis, cerebral thrombosis Current or previous (within 2 weeks) urinary tract bleeding An inherited hemostatic or thrombotic disorder 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 A requirement for therapeutic anticoagulant or antiplatelet drugs Previously documented history of refractoriness to platelet transfusion secondary to HLA (Human Leukocyte Antigen) antibodies Significant renal impairment (creatinine >1.5 times the upper limit of normal) Pregnant or breast-feeding Unwilling or unable to provide informed consent Participant has ever had a pulmonary embolism, deep vein thrombosis, cerebral thrombosis or has active angina Participant has known history of subarachnoid hemorrhage Participant has acquired disturbances to his/her colour vision Participant has known sensitivity or allergy to Tranexamic Acid or any of its ingredients The current use of oral contraceptive pill (Birth Control Pill), hormonal contraceptives or hormone replacement therapy .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Prophylactic Platelet Transfusions<br>Patients allocated to the prophylactic platelet transfusion group will receive a platelet transfusion when the measured platelet count is less than 10 x 10^9/L. | |
| Experimental: Prophylactic Tranexamic Acid<br>Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral dose of Tranexamic Acid 1 gram three times daily. Tranexamic Acid will start when Platelet count is less than 50 x 10^9/L and continue until platelet engraftment. Patients in this group will not receive routine prophylactic platelet transfusions | Drug: Tranexamic Acid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO (World Health Organization) Bleeding events of Grade 2 or higher |  | daily, up to one month | 
| 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 | 
| 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) | LOS=discharge date - admission date | Length of stay will be measured as the number of days elapsed between hospital admission and hospital discharge dates up to 1 month | 
| Adverse transfusion reactions | Number and type of reactions will be recorded. | daily, up to one month | 
| Bearman Toxicity Score | Validated scoring system to assess toxicity during stem cell transplantation | Day 30 | 
| Infections at Day 30 |  | Day 30 | 
| Quality of Life measurements, as determined by a battery of QoL instruments |  | daily, up to one month |