TRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia

NHS Blood and Transplant616 enrolled

Overview

The purpose of this study is to test whether giving tranexamic acid to patients receiving treatment for blood cancers reduces the risk of bleeding or death, and the need for platelet transfusions. Patients will be randomised to receive tranexamic acid (given intravenously through a drip, or orally) or a placebo.

Patients with cancers of the blood often develop low blood cell counts either as a consequence of the disease or the treatment by chemotherapy or stem cell transplantation. Platelet transfusions are commonly given to raise any low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). But recent studies have indicated that many patients continue to experience bleeding, despite the use of platelet transfusions. Tranexamic acid is a type of drug that is called an antifibrinolytic. These drugs act to reduce the breakdown of clots formed in response to bleeding. These drugs have been used widely in both elective and emergency surgery and have been shown to decrease blood loss and the use of red cell transfusions. The purpose of this study is to test whether giving tranexamic acid to patients receiving treatment for blood cancers reduces the risk of bleeding or death, and the need for platelet transfusions. Patients will be randomised to receive tranexamic acid (given intravenously through a drip, or orally) or a placebo. The investigators will measure the rates of bleeding daily using a short structured assessment of bleeding and will record the number of transfusions given to patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Enrollment

616

Conditions

Hematologic Neoplasms Hemorrhage Hematopoietic Stem Cell Transplantation

Interventions

Tranexamic acid (TXA).DRUG

IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid.

PlaceboDRUG

IV (saline) or oral placebo tablets

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Patients are eligible for this trial if: 1. Aged ≥18 years of age 2. Confirmed diagnosis of a haematological malignancy 3. Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation 4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10⁹/L for ≥ 5 days 5. Able to comply with treatment and monitoring Exclusion Criteria: A patient will not be eligible for this trial if he/she fulfils one or more of the following criteria: 1. Patients with a past history or current diagnosis of arterial or venous thromboembolic disease including myocardial infarction, peripheral vascular disease and retinal arterial or venous thrombosis. 2. Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy 3. Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome) 4. Patients with known inherited or acquired prothrombotic disorders e.g. 1. Lupus anticoagulant 2. Positive antiphospholipids 5. Patients receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) within 48 hours of enrolment, or with known hypercoagulable state 6. Patients receiving L-asparaginase as part of their current cycle of treatment 7. History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS) 8. Patients with overt disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition) 9. Patients requiring a platelet transfusion threshold \>10x10/⁹L at time of randomisation. (This refers to patients who require their platelet count to be maintained at a certain specified level on an ongoing basis, and excludes a transient rise in the threshold due to sepsis.) 10. Patients with a known inherited or acquired bleeding disorder e.g. 1. Acquired storage pool deficiency 2. Paraproteinaemia with platelet inhibition 11. Patients receiving anticoagulant therapy or anti-platelet therapy 12. Patients with visible haematuria at time of randomisation 13. Patients with anuria (defined as urine output \< 10 mls/hr over 24 hours). 14. Patients with severe renal impairment (eGFR ≤30 ml/min/1.73m²) 15. Patients with a previous history of epilepsy, convulsions, fits or seizures 16. Patients who are pregnant or breast-feeding 17. Allergic to tranexamic acid. 18. Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents. 19. Patients previously randomised into this trial at any stage of their treatment.

Locations (27)

Royal Adelaide Hospital

Adelaide, Australia

Outcomes

Primary Outcomes

The Proportion of Patients Who Die or Have Bleeding of WHO Grade 2 or Above by WHO Criteria During the First 30 Days From the First Dose of Trial Treatment, or Planned First Dose for Those Participants Who do Not Receive Treatment.

The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment. A time-to-event analysis will be used to determine this proportion to ensure that all patients are included in the primary outcome analysis, not just those who are followed up for the full 30 days. Any patients lost to follow-up will be included in the analysis and censored at the time that they were lost.

Time frame: The first 30 days from first dose of trial treatment

Secondary Outcomes

Mean (SD) Percentage of Days With WHO Grade 2 Bleeding or Above, Per Participant.

Number of days where WHO grade 2 or above bleeding has been recorded bleeding using WHO bleeding criteria.

Time frame: The first 30 days from first dose of trial treatment .

Time to First Episode of Bleeding of WHO Grade 2 or Greater up to Study Day 30.

Bleeding assessed using WHO bleeding criteria. Time to first episode of bleeding of WHO grade 2 or above was estimated using a cumulative incidence function, with death as a competing risk. The lower quartile for the time is reported as the median was not estimable.

Time frame: The first 30 days from first dose of trial treatment.

Highest Grade of Bleeding a Patient Experiences up to Study Day 30.

Measured using WHO bleeding criteria (The higher the grade, the most severe the bleed). Grade 0: no bleeding Grade 1: petechial bleeding Grade 2: mild blood loss (clinically significant) Grade 3: gross blood loss, requires transfusion(severe) Grade 4: debilitating blood loss, retinal or cerebral associated with fatality

Time frame: The first 30 days from first dose of trial treatment.

Data from ClinicalTrials.gov

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