Platelet Transfusions in Hematopoietic Stem Cell Transplantation (The PATH III Trial)

Hematologic Neoplasms Clinical Trial

— PATH  

Official title:

Platelet Transfusions in Hematopoietic Stem Cell Transplantation - The PATH Phase III Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04448184
• Other study ID #: 2068
• Status: Recruiting
• Phase: Phase 3
• Start date: February 16, 2022
• Est. completion date: February 2027

Study information

• Verified date: September 2023
• Source: Ottawa Hospital Research Institute
• Contact: Sohail Robert, RN
• Phone: 613-737-8899
• Email: sorobert[@]ohri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 662
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms

Intervention

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 medication will be administered intravenously.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	Hamilton Health Sciences - Juravinski Hospital and Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Hopital Maisonneuve-Rosemont	Montréal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Eastern Regional Health Authority	Saint John's	Newfoundland and Labrador
Canada	Saskatchewan Cancer Agency	Saskatoon	Saskatchewan
Canada	Memorial University	St. John's	Newfoundland and Labrador
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Alberta Cancer Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	WHO (World Health Organization) bleeding events of Grade 2 or higher		Daily, up to 30 days
Secondary	WHO bleeding events of Grade 3 or 4		Daily, up to 30 days
Secondary	Time from randomization to bleeding of WHO events Grade 2 or higher		Daily, up to 30 days
Secondary	Number of days with bleeding of WHO bleeding events Grade 2 or higher		Daily, up to 30 days
Secondary	Bleeding Severity Measurement Scale (BSMS) for bleeding events Grade 2 or higher	The BSMS scale measures bleeding grade and classification from 0-2. 0 indicates no bleeding. Grade 1 bleeding consists of trace bleeding and mild bleeding and is not clinically significant. Grade 2 bleeding consists of serious bleeding, serious bleeding causing significant morbidity, and fatal bleeding. Grade 2 bleeding is clinically significant.	Daily, up to 30 days
Secondary	Number of platelet and/or red blood cell transfusions		Daily, up to 30 days
Secondary	Adverse reactions related to tranexamic acid	Number and type of reactions will be recorded.	Daily, up to 30 days.
Secondary	Venous thromboembolism grade 2 or higher		Daily, up to 30 days.
Secondary	Adverse reactions related to platelet transfusion	Number and type of reactions will be recorded.	Daily, up to 30 days.
Secondary	Time to platelet count recovery		Daily, up to 30 days.
Secondary	Number of days with a platelet count < 10 x 109/L		Daily, up to 30 days.
Secondary	LOS (Length of hospital stay)	LOS = admission date - discharge date	LOS will be measured as the number of days elapsed between hospital admission and hospital discharge date up to 30 days.
Secondary	Transplant related outcome: Bearman Scoring System for Organ Toxicity following HSCT	This is a validated scoring system to assess toxicity during HSCT. In this system, grade I toxicity is reversible without treatment and grade 2 is not life threatening, but requires treatment. Grade 3 requires life-support intervention and grade 4 is fatal. Regimen-related toxicity in each organ system was scored as the highest grade achieved in that organ system through day 28, except that deaths occurring after day 28 as a result of regimen-related toxicity occurring before day 28 are also scored as grade 4. Adverse events that could be attributed to infection (culture-documented), bleeding or other medications are not scored as regimen-related toxicity. The maximum toxicity is the highest grade recorded in any individual organ system and the cumulative toxicity score is the sum of the highest grades recorded for all eight organ systems.	Day 30
Secondary	Transplant related outcome: Incidence of infections at Day 30 following ASCT		Day 30
Secondary	Transplant related outcome: Mortality at Day 30 and 180		Day 30, Day 180
Secondary	Economic Analyses	Incremental cost effectiveness ratios	5 years
Secondary	Quality of Life Measure: FACT-Thrombocytopenia 18	The FACT consists of 5 subscales that measure physical well-being, functional well-being, social/family well-being and emotional well-being. The BMT subscale of the FACT includes additional items specifically designed to test quality of life and symptoms specific to transplant patients.	Weekly, up to 30 days
Secondary	Quality of Life Measure: FACT- BMT	The FACT-BMT scale is valid and sensitive to clinical change in transplant recipients. It is the most consistently used scale amongst the Canadian Bone Marrow Transplant Group (CBMTG). It is the preferred scale in several Canadian multicentre trials in stem cell transplantation. FACT- Thrombocytopenia 18 is valid measure to elicit quality of life due to thrombocytopenia, and will complement the FACT-BMT scale.	Day 30, Day 90, Day 180
Secondary	Quality of Life Measure: GAD-7	GAD-7 is a short validated scale that assesses symptoms of generalized anxiety and is commonly used in medical settings. There is no specific validated scale to assess anxiety of patients who are at risk for bleeding.	Weekly, up to 30 days
Secondary	Quality of Life Measure: EQ-5D	EQ-5D is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. It is applicable to a wide range of health conditions and treatments; it provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care. It is cognitively undemanding, taking only a few minutes to complete.	Weekly, up to 30 days