To the Editor Compared with placebo, the nonadrenergic vasopressor angiotensin II was shown to increase mean arterial pressure after 3 hours in patients with vasodilatory shock in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial (primary end point). 1 In addition, angiotensin II also reached the secondary goal of a greater reduction in the cardiovascular Sequential Organ Failure Assessment (SOFA) score after 48 hours vs placebo. As a consequence, research with angiotensin II continued and it was approved by the US Food and Drug Administration.In the Selepressin Evaluation Program for Sepsis-Induced Shock-Adaptive Clinical Trial (SEPSIS-ACT), the nonadrenergic vasopressor selepressin, compared with placebo, did not result in improvement in the primary outcome (ventilator-and vasopressor-free days) or in any of the secondary end points (90-day mortality, kidney replacement therapy-free days, intensive care unit-free days) in patients with septic shock. 2 Thus, the first question: Is selepressin a less effective nonadrenergic vasopressor than angiotensin II? No answer can be provided based on 2 different studies evaluating only 1 of the compounds. Nevertheless, the differences in attainment of the respective primary and secondary end points are suggestive.The second question is: Did the authors of the SEPSIS-ACT trial choose the wrong end points? Selepressin treatment not only resulted in an increased mean arterial pressure for up to 6 hours, it also decreased norepinephrine requirements and reduced cardiovascular SOFA scores at 24 and 48 hours compared with placebo. In addition, in agreement with preclinical studies, 3,4 urine output was increased and positive fluid balance reduced after 24 hours. Considering the importance of kidney dysfunction and fluid accumulation in patients with septic shock, these results may be relevant.The final question is: What is the destiny of selepressin? Research with selepressin ended after SEPSIS-ACT stopped recruiting. We hope that the authors point out the numerous positive effects of selepressin that deserve further investigation before another promising drug for septic shock therapy is discarded.