Clinical trial NCT04448184: Platelet Transfusions in Hematopoietic Stem Cell Transplantation (The PATH III Trial)
Official title: Platelet Transfusions in Hematopoietic Stem Cell Transplantation - The PATH Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hematologic Neoplasms
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Alberta Cancer Foundation
First posted: 2020-06-25
Enrollment: 662
Sex: ALL
Minimum age (years): 18
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 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.

Eligibility criteria: Inclusion Criteria:

1. Adults 18 years or older undergoing ASCT for a hematologic malignancy
2. Patients providing written informed consent prior to starting transplantation

Exclusion Criteria:

1. A previous WHO grade 2, 3 or 4 bleeding event within the past year
2. A previous or current unprovoked thrombotic event defined as a pulmonary embolism, deep vein thrombosis, cerebral thrombosis
3. A current provoked thrombotic event (e.g. catheter-related thrombosis) within last month and/or still requiring anticoagulant treatment.
4. A requirement for therapeutic anticoagulant or anti-platelet drugs during ASCT
5. Active angina (chest pain of presumed cardiac origin either at rest or with activity)
6. Current or previous (within 2 weeks) urinary tract bleeding
7. An inherited hemostatic or thrombotic disorder
8. 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
9. 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)
10. 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)
11. Pregnant or breast-feeding
12. Unwilling or unable to provide informed consent
13. Participant has acquired disturbances to his/her colour vision (does not apply to congenital colour blindness)
14. Participant has known sensitivity or allergy to Tranexamic Acid or any of its ingredients

Primary outcomes:
measure: WHO (World Health Organization) bleeding events of Grade 2 or higher
timeFrame: Daily, up to 30 days
Secondary outcomes:
measure: WHO bleeding events of Grade 3 or 4
timeFrame: Daily, up to 30 days
measure: Time from randomization to bleeding of WHO events Grade 2 or higher
timeFrame: Daily, up to 30 days
measure: Number of days with bleeding of WHO bleeding events Grade 2 or higher
timeFrame: Daily, up to 30 days
measure: Bleeding Severity Measurement Scale (BSMS) for bleeding events Grade 2 or higher
timeFrame: Daily, up to 30 days
measure: Number of platelet and/or red blood cell transfusions
timeFrame: Daily, up to 30 days
measure: Adverse reactions related to tranexamic acid
timeFrame: Daily, up to 30 days.
measure: Venous thromboembolism grade 2 or higher
timeFrame: Daily, up to 30 days.
measure: Adverse reactions related to platelet transfusion
timeFrame: Daily, up to 30 days.
measure: Time to platelet count recovery
timeFrame: Daily, up to 30 days.
measure: Number of days with a platelet count < 10 x 109/L
timeFrame: Daily, up to 30 days.
measure: LOS (Length of hospital stay)
timeFrame: LOS will be measured as the number of days elapsed between hospital admission and hospital discharge date up to 30 days.
measure: Transplant related outcome: Bearman Scoring System for Organ Toxicity following HSCT
timeFrame: Day 30
measure: Transplant related outcome: Incidence of infections at Day 30 following ASCT
timeFrame: Day 30
measure: Transplant related outcome: Mortality at Day 30 and 180
timeFrame: Day 30, Day 180
measure: Economic Analyses
timeFrame: 5 years
measure: Quality of Life Measure: FACT-Thrombocytopenia 18
timeFrame: Weekly, up to 30 days
measure: Quality of Life Measure: FACT- BMT
timeFrame: Day 30, Day 90, Day 180
measure: Quality of Life Measure: GAD-7
timeFrame: Weekly, up to 30 days
measure: Quality of Life Measure: EQ-5D
timeFrame: Weekly, up to 30 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Saint John's
country: Canada
facility: Eastern Regional Health Authority
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Memorial University
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
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
city: Montréal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatchewan Cancer Agency
state: Saskatchewan
Study officials:
References: