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

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-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.

• Authors: Richard Onalo, Peter Cooper, Antoinette Cilliers, Barend C Vorster, Nnebe-Agumadu Uche, Oniyangi O Oluseyi, Victoria D Onalo, Yunusa Zubairu, Alice U Ayodele-Kehinde, Oladimeji M Damilare, Janet Figueroa, Claudia R Morris
• Journal: American journal of hematology (Am J Hematol) Vol. 96 Issue 1 Pg. 89-97 (01 2021) ISSN: 1096-8652 [Electronic] United States
• PMID: 33075179 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Arginine

Topics

• Acute Chest Syndrome (drug therapy, economics)
• Administration, Oral
• Adolescent
• Arginine (administration & dosage, economics)
• Child
• Child, Preschool
• Double-Blind Method
• Female
• Humans
• Length of Stay
• Male
• Nigeria
• Prospective Studies