Platelet Transfusion Requirements in Hematopoietic Transplantation Pilot Study (PATH)

Platelet Transfusion Requirements in Hematopoietic Transplantation(PATH Pilot)

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).

Study Overview

• Status: Completed
• Conditions: Hematologic Neoplasms
• Intervention / Treatment: Drug: Tranexamic Acid

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N2
      • Tom Baker Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Hamilton Health Sciences - Juravinski Hospital and Cancer Centre
    • London, Ontario, Canada, N6A5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Prophylactic Platelet Transfusions; 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.
Experimental: Prophylactic Tranexamic Acid; 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	Drug: Tranexamic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Enrolment, as measured by the number of patients screened per month at each site	monthly, up to 23 months
Number of off-protocol platelet transfusions, with a target of < 10% off-protocol transfusions in each treatment arm	monthly, up to 23 months
Total number of platelet transfusions/group, with a target of 25% reduction in the tranexamic acid arm	monthly, up to 23 months
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
WHO (World Health Organization) Bleeding events of Grade 2 or higher		daily, up to one month
Time from randomization to bleeding of WHO bleeding events Grade 2 or higher		daily, up to one month
Number of days with bleeding of WHO bleeding events Grade 2 or higher		daily, up to one month
Bleeding Severity Measurement Scale for bleeding events Grade 2 or higher		daily, up to one month
Number of platelet and/or red cell transfusions		daily, up to one month
Time to platelet recovery		daily, up to one month
Number of days with platelet count < 10 x 10^9/L		daily, up to one month
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
Adverse transfusion reactions	Number and type of reactions will be recorded.	daily, up to one month
Bearman Toxicity Score	Validated scoring system to assess toxicity during stem cell transplantation	Day 30
Infections at Day 30		Day 30
Quality of Life measurements, as determined by a battery of QoL instruments		daily, up to one month

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Alan Tinmouth, MD MSc, Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: January 6, 2016
• First Submitted That Met QC Criteria: January 6, 2016
• First Posted (Estimate): January 8, 2016

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 20150629-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No