Patients with haematological malignancies receiving intensive chemotherapy and/or stem cell transplantation Cancer
Conditions
Interventions
Prophylactic TXA/Placebo, double-blind, placebo controlled parallel group trial to assess the safety and efficacy of tranexamic acid at reducing bleeding in patients with haematological malignancies a
Study Entry : Single Randomisation only
Sponsors
NHS Blood and Transplant (NHSBT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years of age 2. Confirmed diagnosis of a haematological malignancy 3. Undergoing chemotherapy or haematopoietic stem cell transplantation 4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of =10x10 to the power of 9/L for = 5 days 5. Able to comply with treatment and monitoring
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 10/12/2018: 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. 4.1. Lupus anticoagulant 4.2. 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 DIC (See Appendix 3 in the protocol for definition) 9. Patients requiring a platelet transfusion threshold >10x109/L 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. 10.1. Acquired storage pool deficiency 10.2. 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 10x10 to the power of 9/L at time of randomisation 13. Patients with anuria (defined as urine output < 10mls/hr over 24 hours) 14. Patients who are pregnant 15. Patients en
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 10/12/2018: Estimated proportion of participants who died or had bleeding of WHO grade 2 or above during the first 30 days of the trial from the first day of trial treatment. A time-to-event analysis will be used to determine this proportion to ensure that all participants are included in the primary outcome analysis, not just those who are followed up for the full 30 days. Any participants lost to follow-up will be included in the analysis and censored at the time that they were lost. Previous primary outcome measure: Proportion of patients who died or had bleeding of WHO grade 2 or above during the first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to =30x109/L. 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 10/12/2018: 1. Secondary Efficacy Outcomes: All measured during first 30 days of the trial, i.e. from the first day of trial treatment. 1.1. Proportion of days with bleeding (WHO grade 2 or above) 1.2. Time to first episode of bleeding of WHO grade 2 or greater 1.3. Highest grade of bleeding a participant experiences 1.4. Number of platelet transfusions/participant 1.5. Number of red cell transfusions/participant 1.6. Proportion of participants surviving up to 30 days without a platelet transfusion 1.7. Proportion of participants surviving up to 30 days without a red cell transfusion 1.8. Quality of life, measured using EQ-5D-5L and FACT-TH18 (V4) at Day of Randomisation, Day 12, Day 30 and Day 120 2. Secondary Safety Outcomes: 2.1. Number of thrombotic events from first administration of trial treatment up to and including 120 days after the first dose of trial treatment is administered, per day at risk 2.2. Number of participants developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment 2.3. All-cause mortality during the first 30 days and the first 120 days after the first dose of trial treatment is administered 2.4. Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered 2.5. Death due to bleeding during the first 30 days after the first dose of trial treatment is administered 2.6. Number of serious adverse events from first administration of trial treatment until 60 days after the first dose of trial treatment is administered 3. Other outcomes: All measured during first 30 days of the trial, i.e. from the first dose of trial treatment 3.1. Proportion of days with thrombocytopenia (=10x109/L, =30x109/L, =50x109/L) 3.2. Proportion of days with fever (highest daily temperature = 38.1°C) of days spent in hospital, up to study day 30 3.3. Reasons for platelet and red cell transfusions Previous | — |
Countries
Australia, England, United Kingdom
Outcome results
None listed