Tranexamic acid versus placebo to prevent bleeding in patients with haematological malignancies and severe thrombocytopenia (TREATT): a randomised, double-blind, parallel, phase 3 superiority trial

Background: Bleeding is common in patients with haematological malignancies undergoing intensive therapy. We aimed to assess the effect of tranexamic acid on preventing bleeding and the need for platelet transfusions. Methods: TREATT was an international, randomised, double-blind, parallel, phase 3 superiority trial conducted at 27 haematology centres in Australia and the UK. We enrolled adults (aged ≥18 years) receiving intensive chemotherapy or haematopoietic stem-cell transplantation for a haematological malignancy, with a platelet count of 10 × 10⁹ platelets per L or less for 5 days or longer. Patients were randomly assigned (1:1) using block randomisation, stratified by site, to tranexamic acid (1 g every 8 h intravenously or 1·5g every 8 h orally) or placebo when their platelet count was less than 30 × 10⁹ platelets per L. Treatment was continued until platelet recovery or day 30. Prophylactic platelet transfusions were maintained as standard of care. The primary endpoint was the proportion of patients who died or had WHO grade 2 or higher bleeding up to day 30. A modified intention-to-treat population including randomly assigned patients whose platelet count decreased to 30 × 10⁹ platelets per L or less was used for analysis. This trial is registered with ClinicalTrials.gov (NCT03136445), ISRCTN (ISRCTN73545489), and the European Clinical Trials Register (EudraCT 2014-001513-35). Findings: Between June 23, 2015, and Feb 17, 2022, 1736 patients were screened for eligibility, 616 of whom were enrolled and randomly assigned (310 to tranexamic acid and 306 to placebo). 19 participants were excluded from the modified intention-to-treat analysis, leaving 300 participants in the tranexamic acid group and 297 in the placebo group. Participant median age was 58 years (IQR 49–65), 380 (62%) of 616 participants were male, and 235 (38%) were female. The proportion of participants who died or had WHO grade 2 or higher bleeding was 31·7% (90/298 [95% CI 26·6–37·4]) in the tranexamic acid group and 34·2% (98/295 [29·0–40·0]) in the placebo group (hazard ratio 0·92 [95% CI 0·67–1·27]; p=0·62). There were no differences in thrombotic events or veno-occlusive disease. 94 serious adverse events in 77 participants were reported up to day 60 in the tranexamic acid group and 103 events in 82 participants in the placebo group. Interpretation: There is insufficient evidence to support routine use of tranexamic acid to reduce bleeding in patients with haematological malignancies undergoing intensive chemotherapy. Funding: UK National Health Service Blood and Transplant and Australian National Health and Medical Research Council.