Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
The TOP-ART trial aimed to determine the safety and efficacy of intravenous artesunate in reducing multiple organ dysfunction syndrome (MODS) in trauma patients with major hemorrhage. The trial, however, was terminated early due to safety concerns after enrolling 90 out of the targeted 105 patients. In the 83 patients who received either artesunate (n=54) or placebo (n=29), it was found that serious adverse events (SAEs) were more common in the artesunate group, with 31% (n=17) of patients experiencing SAEs compared to 17% (n=5) in the placebo group.
Furthermore, 17% of the artesunate group experienced venous thromboembolic events (VTE) compared to just 3% in the placebo group. There was no statistical evidence supporting the superiority of artesunate in improving organ dysfunction as measured by the 48-hour SOFA score. The median score was 5.5 for the artesunate group compared to 4 for the placebo group (p=0.303).
Artesunate recipients had a more profound shock, as indicated by a higher median base deficit (9 vs. 4.7, p=0.042). Given these findings, artesunate is unlikely to improve organ dysfunction in this patient population and might be associated with a higher rate of VTE.