Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in Nigeria

Low arginine bioavailability is associated with vaso‐occlusive painful crisis (VOC) severity in sickle cell anemia (SCA) and predicts need for pediatric hospitalization. Intravenous arginine therapy has opioid‐sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA‐VOC in a phase‐two randomized placebo‐controlled trial (RCT). Efficacy of oral arginine is unknown. Our objective was to determine the safety and efficacy of oral arginine therapy in Nigerian children with SCA. A double‐blind RCT of oral L‐arginine‐hydrochloride (100 mg/kg TID) was conducted in children with SCA‐VOC, aged 5‐17 years, hospitalized at two Nigerian sites. The primary outcome measure was analgesic usage, quantified by difference in the mean Analgesic Medication Quantification Scale (MQS). Secondary outcomes included daily pain scores, time‐to‐crisis‐resolution and length‐of‐hospital‐stay. An intention‐to‐treat analysis was performed. Sixty‐eight children (age 5‐17 years, mean 10.6 ± 0.4 years; 56% male), were randomized to receive L‐arginine (35 patients) or placebo (33 patients). The mean total MQS for the arginine group was 73.4 (95% CI, 62.4‐84.3) vs 120.0 (96.7‐143.3) for placebo ( P  < .001). The mean rate of decline in worst pain scores was faster in the arginine arm vs placebo (1.50 [1.23‐1.77] vs 1.09 [0.94‐1.24] point/d, P = .009). Children receiving arginine had a shorter time‐to‐crisis‐resolution ( P = .02), shorter hospital‐stay ( P = .002) and experienced no serious adverse event. Pain control was more rapid, total analgesic requirement was significantly reduced, and most notably, time‐to‐crisis‐resolution and length‐of‐hospital‐stay were shorter in children with SCA‐VOC receiving arginine vs placebo. Given the established safety and low cost, oral arginine is a promising adjuvant therapy for SCA‐VOC management.