Clinical trial NCT02650791: Platelet Transfusion Requirements in Hematopoietic Transplantation Pilot Study
Official title: Platelet Transfusion Requirements in Hematopoietic Transplantation(PATH Pilot)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hematologic Neoplasms
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2016-01-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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 .

Primary outcomes:
measure: Enrolment, as measured by the number of patients screened per month at each site
timeFrame: monthly, up to 23 months
measure: Number of off-protocol platelet transfusions, with a target of < 10% off-protocol transfusions in each treatment arm
timeFrame: monthly, up to 23 months
measure: Total number of platelet transfusions/group, with a target of 25% reduction in the tranexamic acid arm
timeFrame: monthly, up to 23 months
measure: Adherence to tranexamic acid use, defined as excellent (greater than or equal to 90% use), acceptable (75-90% use), poor (< 75% use)
timeFrame: monthly, up to 23 months
Secondary outcomes:
measure: WHO (World Health Organization) Bleeding events of Grade 2 or higher
timeFrame: daily, up to one month
measure: Time from randomization to bleeding of WHO bleeding events Grade 2 or higher
timeFrame: daily, up to one month
measure: Number of days with bleeding of WHO bleeding events Grade 2 or higher
timeFrame: daily, up to one month
measure: Bleeding Severity Measurement Scale for bleeding events Grade 2 or higher
timeFrame: daily, up to one month
measure: Number of platelet and/or red cell transfusions
timeFrame: daily, up to one month
measure: Time to platelet recovery
timeFrame: daily, up to one month
measure: Number of days with platelet count < 10 x 10^9/L
timeFrame: daily, up to one month
measure: LOS (Length of hospital stay)
timeFrame: Length of stay will be measured as the number of days elapsed between hospital admission and hospital discharge dates up to 1 month
measure: Adverse transfusion reactions
timeFrame: daily, up to one month
measure: Bearman Toxicity Score
timeFrame: Day 30
measure: Infections at Day 30
timeFrame: Day 30
measure: Quality of Life measurements, as determined by a battery of QoL instruments
timeFrame: daily, up to one month
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Hospital and Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Alan Tinmouth, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tay J, Allan D, Beattie S, Bredeson C, Fergusson D, Maze D, Sabloff M, Thavorn K, Tinmouth A. Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study. BMJ Open. 2016 Oct 24;6(10):e013483. doi: 10.1136/bmjopen-2016-013483.