No evidence of benefit
Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.
A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).
Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.
The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.
The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.
In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).
Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).
There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).
“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.
A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”
Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.
There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.
The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
