Platelet Transfusion Requirements in Hematopoietic Transplantation Pilot Study

Hematologic Neoplasms Clinical Trial

— PATH  

Official title:

Platelet Transfusion Requirements in Hematopoietic Transplantation(PATH Pilot)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02650791
• Other study ID #: 20150629-01H
• Status: Completed
• Phase: Phase 3
• Start date: October 2016
• Est. completion date: December 2019

Study information

• Verified date: May 2020
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 .

Related Conditions & MeSH terms

• Hematologic Neoplasms

Intervention

Drug:
• Tranexamic Acid

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Hamilton Health Sciences - Juravinski Hospital and Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Enrolment, as measured by the number of patients screened per month at each site		monthly, up to 23 months
Primary	Number of off-protocol platelet transfusions, with a target of < 10% off-protocol transfusions in each treatment arm		monthly, up to 23 months
Primary	Total number of platelet transfusions/group, with a target of 25% reduction in the tranexamic acid arm		monthly, up to 23 months
Primary	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	WHO (World Health Organization) Bleeding events of Grade 2 or higher		daily, up to one month
Secondary	Time from randomization to bleeding of WHO bleeding events Grade 2 or higher		daily, up to one month
Secondary	Number of days with bleeding of WHO bleeding events Grade 2 or higher		daily, up to one month
Secondary	Bleeding Severity Measurement Scale for bleeding events Grade 2 or higher		daily, up to one month
Secondary	Number of platelet and/or red cell transfusions		daily, up to one month
Secondary	Time to platelet recovery		daily, up to one month
Secondary	Number of days with platelet count < 10 x 10^9/L		daily, up to one month
Secondary	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
Secondary	Adverse transfusion reactions	Number and type of reactions will be recorded.	daily, up to one month
Secondary	Bearman Toxicity Score	Validated scoring system to assess toxicity during stem cell transplantation	Day 30
Secondary	Infections at Day 30		Day 30
Secondary	Quality of Life measurements, as determined by a battery of QoL instruments		daily, up to one month