Bardhan Pradip Kumar, Das Rina, Nahar Baitun, Haque Md Ahshanul, Sobi Rukaeya Amin, Sultana Al-Afroza, Mahfuz Mustafa, Fawkes Neil, Smith Adam B, Vidyasagar Sadasivan, Fontaine Olivier, Ahmed Tahmeed
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh.
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta GA-30322, USA.
EClinicalMedicine. 2024 May 17;72:102630. doi: 10.1016/j.eclinm.2024.102630. eCollection 2024 Jun.
Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy (ORT), its adoption remains low. Glucose-based ORS (GORS) is the standard, but novel formulations like glucose-free amino acid-based VS002A have emerged as potential alternatives. This study aimed to compare the safety and efficacy of VS002A against the standard WHO-ORS in treating non-cholera acute watery diarrhoea in children.
A triple-blind, randomized trial enrolled 310 male infants and children aged 6-36 months, who were assigned to receive WHO-ORS or VS002A over a 16-month period, from June 2021 to September 2022. Both groups received standard of care, including zinc supplementation. The Primary study outcome measured was the duration of diarrhoea. Secondary outcomes included stool output, treatment failure and adverse events. Exploratory endpoints included urinary output, body weight changes, blood biochemistry, stool microbiology and gut health biomarkers.
Both VS002A and WHO-ORS were well-tolerated with a low adverse event rate. While not different statistically (p = 0.10), duration of diarrhoea was shorter in children treated with VS002A vs. WHO-ORS (65.4 h vs. 72.6 h). Similarly, stool output was also lower vs. WHO-ORS in children treated with VS002A, though not statistically different (p = 0.40). Serum citrulline levels, an indicator of gut health, were higher in the VS002A group at 24 h suggesting a potential protective effect (p = 0.06).
The findings of this study support the non-inferiority of VS002A, a glucose-free amino acid-based ORS compared to the WHO-ORS standard of care. VS002A was shown to be safe and effective in treating non-cholera acute watery diarrhoea in young children. VS002A may offer advantages in pathogen-driven diarrhoea, supported by trends toward a lower duration of diarrhoea and stool output within the per protocol group. Furthermore, individuals with prolonged diarrhoea, severe malnutrition, environmental enteric dysfunction or have issues with obesity or insulin resistance, could benefit from a glucose-free ORS. This research contributes to addressing the persistent challenge of childhood diarrhoea by presenting an alternative glucose-free ORS formulation with potential advantages in select scenarios, offering a promising avenue for improving paediatric diarrhoea management worldwide.
The study was funded by Entrinsic Bioscience, LLC., Norwood, MA, USA.
腹泻病是一项重大的全球健康挑战，尤其对三岁以下儿童而言。尽管口服补液疗法（ORT）有效，但其采用率仍然很低。基于葡萄糖的口服补液盐（GORS）是标准疗法，但诸如无葡萄糖氨基酸基VS002A等新型制剂已成为潜在的替代方案。本研究旨在比较VS002A与世界卫生组织标准口服补液盐（WHO-ORS）在治疗儿童非霍乱急性水样腹泻方面的安全性和有效性。
一项三盲随机试验纳入了310名6至36个月大的男童和女童，在2021年6月至2022年9月的16个月期间，他们被分配接受WHO-ORS或VS002A治疗。两组均接受包括补锌在内的标准治疗。测量的主要研究结局是腹泻持续时间。次要结局包括粪便排出量、治疗失败和不良事件。探索性终点包括尿量、体重变化、血液生化、粪便微生物学和肠道健康生物标志物。
VS002A和WHO-ORS的耐受性均良好，不良事件发生率较低。虽然腹泻持续时间在统计学上无差异（p = 0.10），但接受VS002A治疗的儿童腹泻持续时间比接受WHO-ORS治疗的儿童短（65.4小时对72.6小时）。同样，接受VS002A治疗的儿童粪便排出量也比接受WHO-ORS治疗的儿童低，尽管在统计学上无差异（p = 0.40）。作为肠道健康指标的血清瓜氨酸水平在24小时时在VS002A组中较高，表明可能具有保护作用（p = 0.06）。
本研究结果支持与WHO-ORS标准治疗相比，无葡萄糖氨基酸基ORS的VS002A具有非劣效性。VS002A在治疗幼儿非霍乱急性水样腹泻方面被证明是安全有效的。在符合方案组中，腹泻持续时间和粪便排出量有缩短趋势，这表明VS002A在病原体驱动的腹泻中可能具有优势。此外，腹泻持续时间长、严重营养不良、患有环境肠道功能障碍或有肥胖或胰岛素抵抗问题的个体，可能会从无葡萄糖口服补液盐中受益。本研究通过提出一种在特定情况下具有潜在优势的无葡萄糖口服补液盐替代制剂，为应对儿童腹泻这一持续挑战做出了贡献，为改善全球儿童腹泻管理提供了一条有前景的途径。
本研究由美国马萨诸塞州诺伍德的Entrinsic Bioscience, LLC.资助。
