A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis.

The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) were randomized and 320 were treated (162 with rivipansel, 158 with placebo) with an IV loading dose, followed by up to 14 additional 12-hourly maintenance doses of rivipansel or placebo, in addition to standard care. Rivipansel was similarly administered during subsequent VOCs in the Open-label Extension (OLE) study. In the full analysis population, the median time to readiness for discharge (TTRFD), the primary end point, was not different between rivipansel and placebo (-5.7 hours, P = .79; hazard ratio, 0.97), nor were differences seen in secondary end points of time to discharge (TTD), time to discontinuation of IV opioids (TTDIVO), and cumulative IV opioid use. Mean soluble E-selectin decreased 61% from baseline after the loading dose in the rivipansel group, while remaining unchanged in the placebo group. In a post hoc analysis, early rivipansel treatment within 26.4 hours of VOC pain onset (earliest quartile of time from VOC onset to treatment) reduced median TTRFD by 56.3 hours, reduced median TTD by 41.5 hours, and reduced median TTDIVO by 50.5 hours, compared with placebo (all P < .05). A similar subgroup analysis comparing OLE early-treatment with early-treatment RESET placebo showed a reduction in TTD of 23.1 hours (P = .062) and in TTDIVO of 30.1 hours (P = .087). Timing of rivipansel administration after pain onset may be critical to achieving accelerated resolution of acute VOC. Trial Registration: Clinicaltrials.gov, NCT02187003 (RESET), NCT02433158 (OLE).

Peripheral arterial tonometry in assessing endothelial dysfunction in pediatric sickle cell disease.

BACKGROUND: SCD is characterized by hemolysis and oxidative stress, resulting in endothelial dysfunction (EDF). Peripheral arterial tonometry (PAT), a noninvasive technology for measuring EDF, utilizes reactive hyperemia following mini-ischemic stress (reactive hyperemia index or RHI). METHODS: The authors studied PAT in 36 SCD children to determine the influence of hemoglobin genotype and treatment on EDF. RESULTS AND CONCLUSIONS: Blunted RHI was seen in the majority of children with SCD, especially with increased symptomatology (1.53 and 1.71; p value .032). RHI was not normal in children on chronic transfusion or hydroxyurea. RHI correlated with reticulocyte fraction (Spearman r = -.47, p = .037). PAT merits further exploration as a measure of EDF in SCD.