Intravenous Arginine Did Not Shorten Sickle Cell Pain Crises in Phase 3 Trial

Acute pain episodes are a leading cause of emergency visits and hospitalizations in sickle cell disease (SCD), and earlier phase 2 trials suggested benefits from arginine supplementation. This prospective, double-blind phase 3 trial enrolled 274 patients aged 3–21 years at 10 US children’s hospitals between June 2021 and June 2024. Participants required parenteral opioids and were randomized to intravenous arginine or saline placebo. The primary endpoint was time from the first study dose to the last intravenous opioid dose.

Of those randomized, 271 received study treatment: 129 received arginine and 142 received placebo. Mean age was 14.3 years. The trial was halted early for futility. Median time to crisis resolution was 60.8 hours with arginine versus 65.8 hours with placebo; the reported absolute difference was 7.2 hours (95% CI, −21.6 to 35.9). There were no significant differences in total parenteral opioid use, pain scores, patient-reported outcomes, or safety events.

These findings do not support intravenous arginine for shortening acute SCD pain crises in this population, despite encouraging earlier trials. Early termination and the wide confidence interval should inform interpretation; the absence of a significant safety difference does not establish equivalence. Full-text details were not available in the supplied source.