Platelet Transfusion Requirements in Hematopoietic Transplantation Pilot Study (PATH)

Ottawa Hospital Research Institute

Status and phase: Completed; Phase 3

Conditions: Hematologic Neoplasms

Treatments: Drug: Tranexamic Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT02650791

20150629-01H

Details and patient eligibility

About

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).

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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 .

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Prophylactic Platelet Transfusions

No Intervention group

Description:

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.

Prophylactic Tranexamic Acid

Experimental group

Description:

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

Treatment:

Drug: Tranexamic Acid