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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04448184
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : July 1, 2022
Sponsor:
Collaborator:
Alberta Cancer Foundation
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

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).

Condition or disease Intervention/treatment Phase
Hematologic Neoplasms Drug: Tranexamic Acid Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 662 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Platelet Transfusions in Hematopoietic Stem Cell Transplantation - The PATH Phase III Trial
Actual Study Start Date : February 16, 2022
Estimated Primary Completion Date : February 2027
Estimated Study Completion Date : February 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Prophylactic Platelet Transfusion
Patients allocated to the prophylactic platelet transfusion group will receive a platelet transfusion when the measured platelet count is less than 10 x 109/L.
Experimental: Prophylactic 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.
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.

Other Names:
  • SteriMax Inc.
  • Cyclokapron®




Primary Outcome Measures :
  1. WHO (World Health Organization) bleeding events of Grade 2 or higher [ Time Frame: Daily, up to 30 days ]

Secondary Outcome Measures :
  1. WHO bleeding events of Grade 3 or 4 [ Time Frame: Daily, up to 30 days ]
  2. Time from randomization to bleeding of WHO events Grade 2 or higher [ Time Frame: Daily, up to 30 days ]
  3. Number of days with bleeding of WHO bleeding events Grade 2 or higher [ Time Frame: Daily, up to 30 days ]
  4. Bleeding Severity Measurement Scale (BSMS) for bleeding events Grade 2 or higher [ Time Frame: Daily, up to 30 days ]
    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.

  5. Number of platelet and/or red blood cell transfusions [ Time Frame: Daily, up to 30 days ]
  6. Adverse reactions related to tranexamic acid [ Time Frame: Daily, up to 30 days. ]
    Number and type of reactions will be recorded.

  7. Venous thromboembolism grade 2 or higher [ Time Frame: Daily, up to 30 days. ]
  8. Adverse reactions related to platelet transfusion [ Time Frame: Daily, up to 30 days. ]
    Number and type of reactions will be recorded.

  9. Time to platelet count recovery [ Time Frame: Daily, up to 30 days. ]
  10. Number of days with a platelet count < 10 x 109/L [ Time Frame: Daily, up to 30 days. ]
  11. 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. ]
    LOS = admission date - discharge date

  12. Transplant related outcome: Bearman Scoring System for Organ Toxicity following HSCT [ Time Frame: Day 30 ]
    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.

  13. Transplant related outcome: Incidence of infections at Day 30 following ASCT [ Time Frame: Day 30 ]
  14. Transplant related outcome: Mortality at Day 30 and 180 [ Time Frame: Day 30, Day 180 ]
  15. Economic Analyses [ Time Frame: 5 years ]
    Incremental cost effectiveness ratios

  16. Quality of Life Measure: FACT-Thrombocytopenia 18 [ Time Frame: Weekly, up to 30 days ]
    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.

  17. Quality of Life Measure: FACT- BMT [ Time Frame: Day 30, Day 90, Day 180 ]
    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.

  18. Quality of Life Measure: GAD-7 [ Time Frame: Weekly, up to 30 days ]
    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.

  19. Quality of Life Measure: EQ-5D [ Time Frame: Weekly, up to 30 days ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04448184


Contacts
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Contact: Sohail Robert, RN 613-737-8899 ext 71892 sorobert@ohri.ca
Contact: Alan Tinmouth, MD 613-737-8899 ext 73914 atinmouth@ohri.ca

Locations
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Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N4N2
Contact: Jason Tay, MD    403-944-1880    Jason.Tay@ahs.ca   
Principal Investigator: Jason Tay, MD         
Cross Cancer Institute Not yet recruiting
Edmonton, Alberta, Canada
Contact: Christopher Venner, MD         
Canada, Newfoundland and Labrador
Memorial University Not yet recruiting
St. John's, Newfoundland and Labrador, Canada
Contact: Kirsty Tompkins, MD         
Canada, Nova Scotia
Dalhousie University Not yet recruiting
Halifax, Nova Scotia, Canada
Contact: Mahmood El-Sawy, MD         
Canada, Ontario
Hamilton Health Sciences - Juravinski Hospital and Cancer Centre Not yet recruiting
Hamilton, Ontario, Canada, L8V 1C3
Contact: Irwin Walker, MD    905 521-2100 ext 76384    walkeri@mcmaster.ca   
Principal Investigator: Irwin Walker, MD         
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A5W9
Contact: Anargyros Xenocostas, MD    519-685-8500 ext 58631    Anargyros.Xenocostas@lhsc.on.ca   
Principal Investigator: Anargyros Xenocostas, MD         
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H8L6
Contact: Alan Tinmouth, MD    613-737-8899 ext 73914    atinmouth@ohri.ca   
Principal Investigator: Alan Tinmouth, MD MSc RCPSC         
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Dawn Maze, MD, MSc    416-946-4501 ext 4521    dawn.maze@uhn.ca   
Canada, Quebec
Hopital Maisonneuve-Rosemont Not yet recruiting
Montréal, Quebec, Canada
Contact: Silvy Lachance, MD         
Canada, Saskatchewan
Saskatchewan Cancer Agency Not yet recruiting
Saskatoon, Saskatchewan, Canada
Contact: Mohamed Elementary, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Alberta Cancer Foundation
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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT04448184    
Other Study ID Numbers: 2068
First Posted: June 25, 2020    Key Record Dates
Last Update Posted: July 1, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants