Abstract
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-2 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 (100mg/kg TID) was conducted in children with SCA-VOC, aged 5-17 years, hospitalized at 2 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 5-17years, 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] versus 120.0 [96.7-143.3] for placebo (p<0.001). The mean rate of decline in worst pain scores was faster in the arginine arm versus placebo (1.50 [1.23-1.77] vs. 1.09 [0.94-1.24] point/day, p=0.009). Children receiving arginine had a shorter time-to-crisis-resolution (p=0.02), shorter hospital-stay (p=0.002) 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 versus placebo. Given the established safety and low cost, oral arginine is a promising adjuvant therapy for SCA-VOC management. This article is protected by copyright. All rights reserved.
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