Premature trial determination
deaths
While SAEs and deaths were judged as not related to the trial medication, their increased occurrence in the intervention arm led the DSMB to recommend an interruption of the trial after the second interim analysis. In addition, the DSMB recommended to await the outcome data of this analysis, including analyses of the activity of the plasma cascades prior to further decision-making on cessation or continuation of the trial. Subsequently, the trial was terminated prematurely in September 2021 for the following reasons. First, the intervention regimen was not associated with a significant inhibition of the CS and activation of other plasma cascades or endothelial cells. Second, considering the results in the primary outcome not favoring the intervention and the observed imbalances in the baseline characteristics, a larger sample size would have been required to show a difference if there was a true difference. Third, during the second half of the year 2021, additional treatment options such as anti-SARS-CoV-2 monoclonal antibodies and tocilizumab were introduced and recommended, making the study groups even more heterogeneous.