Platelet Transfusions in Hematopoietic Stem Cell Transplantation (The PATH III Trial)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Tranexamic Acid.
- Who it may be relevant to
- Registry conditions: Hematologic Neoplasms. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Platelet Transfusions in Hematopoietic Stem Cell Transplantation - The PATH Phase III Trial
Overview
It is hypothesized that a strategy using prophylactic oral and intravenous Tranexamic Acid (TXA) with therapeutic platelet transfusions (if required) is safe and more effective than prophylactic platelet transfusions in patients undergoing an autologous hematopoietic stem cell transplantation (ASCT).
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 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.
A pilot trial demonstrated feasibility by successfully recruiting 100 patients and these patients will be rolled over into the phase III study. The treatment assignment and bleeding outcomes for these patients remain blinded.
Interventions
- Drug Tranexamic Acid
Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral or intravenous dose of Tranexamic Acid 1 gram three times daily. Tranexamic Acid will start when Platelet count is less than 50 x 109/L and continue until platelet engraftment. Patients in this group will not receive routine prophylactic platelet transfusions. Subjects unable to swallow oral Tranexamic Acid pills may have the tablets crushed, administered via nasogastric (NG) tube or the medica
Primary outcome measures
- WHO (World Health Organization) bleeding events of Grade 2 or higher [Time frame: Daily, up to 30 days]
Secondary outcome measures (12)
- WHO bleeding events of Grade 3 or 4 [Time frame: Daily, up to 30 days]
- Time from randomization to bleeding of WHO events Grade 2 or higher [Time frame: Daily, up to 30 days]
- Number of days with bleeding of WHO bleeding events Grade 2 or higher [Time frame: Daily, up to 30 days]
- Bleeding Severity Measurement Scale (BSMS) for bleeding events Grade 2 or higher [Time frame: Daily, up to 30 days]
- Number of platelet and/or red blood cell transfusions [Time frame: Daily, up to 30 days]
- Adverse reactions related to tranexamic acid [Time frame: Daily, up to 30 days.]
- Venous thromboembolism grade 2 or higher [Time frame: Daily, up to 30 days.]
- Adverse reactions related to platelet transfusion [Time frame: Daily, up to 30 days.]
- Time to platelet count recovery [Time frame: Daily, up to 30 days.]
- Number of days with a platelet count < 10 x 109/L [Time frame: Daily, up to 30 days.]
- LOS (Length of hospital stay) [Time frame: LOS will be measured as the number of days elapsed between hospital admission and hospital discharge date up to 30 days.]
- Transplant related outcome: Bearman Scoring System for Organ Toxicity following HSCT [Time frame: Day 30]
Eligibility criteria
Inclusion criteria
- Adults 18 years or older undergoing ASCT for a hematologic malignancy
- Patients providing written informed consent prior to starting transplantation
Exclusion criteria
- A previous WHO grade 2, 3 or 4 bleeding event within the past year
- A previous or current unprovoked thrombotic event defined as a pulmonary embolism, deep vein thrombosis, cerebral thrombosis
- A current provoked thrombotic event (e.g. catheter-related thrombosis) within last month and/or still requiring anticoagulant treatment.
- A requirement for therapeutic anticoagulant or anti-platelet drugs during ASCT
- Active angina (chest pain of presumed cardiac origin either at rest or with activity)
- Current or previous (within 2 weeks) urinary tract bleeding
- An inherited hemostatic or thrombotic disorder
- Coagulopathy defined as a prothrombin time '/International Normalization Ratio (INR) or activated partial thromboplastin time more than 1.5 times the upper limit of normal or fibrinogen less than 2 g/L
- Previously documented history of refractoriness to platelet transfusion secondary to HLA antibodies (Refractoriness is defined as 2 consecutive ABO matched platelet transfusions with platelet increment of < 7.5 and the presence of anti-HLA antibodies)
- Significant renal impairment (creatinine more than 1.5 times the upper limit of normal or a eGFR less than 0.5 mL/min/1.78m2)
- Pregnant or breast-feeding
- Unwilling or unable to provide informed consent
- Participant has acquired disturbances to his/her colour vision (does not apply to congenital colour blindness)
- Participant has known sensitivity or allergy to Tranexamic Acid or any of its ingredients
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Other
Study locations
Canada · 12 centers
- Tom Baker Cancer Centre — Calgary
- Cross Cancer Institute — Edmonton
- Eastern Regional Health Authority — St. John's
- Memorial University — St. John's
- Dalhousie University — Halifax
- Hamilton Health Sciences - Juravinski Hospital and Cancer Centre — Hamilton
- London Health Sciences Centre — London
- The Ottawa Hospital — Ottawa
- … and 4 more centers
Identifiers
NCT: NCT04448184 · 2068