Nagaraja V, Spino C, Bush E, et al. - Individuals with systemic sclerosis (SSc)-related active or painful indeterminate digital ulcer (DU) were enrolled in a multicenter, double-blind, randomized, placebo-controlled, proof-of-concept trial in order to ascertain the impact of riociguat, an oral, selective soluble guanylate cyclase stimulator, on the net DU burden in SSc. Seventeen individuals (eight placeboes, nine riociguat) were randomized at five centers. At baseline, the mean (SD) net ulcer burden (NUB) was 2.5 and 2.4 in the placebo and in the riociguat, respectively. No important treatment variance was noted in the change from baseline to 16 weeks in NUB. Four individuals experienced five serious adverse events (AEs) and none was recognized as correlated to study medication. A statistically significant rise of Cyclic guanylyl cyclase was recognized at 16 weeks in the riociguat group and no other biomarkers exhibited important variations. In the open-label extension, participants in the riociguat-riociguat arm had absolute healing of their DUs. Thus, in participants with SSc-DU, treatment with riociguat did not decrease the number of DU net burden in comparison with placebo at 16 weeks. Open-label extension hints that longer term is required to promote DU healing, which demands to be validated in a new trial.