• 在加拿大6个急诊科,886名3-48月大儿童在确诊胃肠炎后,连续5天(2次/天)摄入4X10^9 cfu 的鼠李糖乳杆菌R0011(95%)和瑞士乳杆菌R0052(5%)二联制剂或安慰剂;
  • 入组14天内,试验组和安慰剂组中仍发生中重度胃肠炎的儿童占比分别为26.1%(108/414)和24.7%(102/413);
  • 两组之间的腹泻(52.5h vs 55.5h)和呕吐(17.7h vs 18.7h)中位持续时间、计划外到医疗机构就医的比例(30.2% vs 26.6%)、报告不良反应的比例(34.8% vs 38.7%)均无显著差异。
这是New England Journal of Medicine [79.258] 刚刚发布的两项重量级益生菌临床随机对照试验结果之一,表明鼠李糖乳杆菌R0011和瑞士乳杆菌R0052二联制剂并无法在14天内预防中重度胃肠炎的持续发生。这是关于益生菌无法有效应对特定适应症的高等级临床研究证据,很值得关注其中的实验设计、临床实施和数据分析方法。

Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis



2018-11-22, Article

Abstract & Authors:展开

BACKGROUND: Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves outcomes in these children are lacking.
METHODS: We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×109 colony-forming units twice daily or placebo. The primary outcome was moderate-to-severe gastroenteritis, which was defined according to a post-enrollment modified Vesikari scale symptom score of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease). Secondary outcomes included the duration of diarrhea and vomiting, the percentage of children who had unscheduled physician visits, and the presence or absence of adverse events.
RESULTS: Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) who were assigned to probiotics and 102 of 413 participants (24.7%) who were assigned to placebo (odds ratio, 1.06; 95% confidence interval [CI], 0.77 to 1.46; P=0.72). After adjustment for trial site, age, detection of rotavirus in stool, and frequency of diarrhea and vomiting before enrollment, trial-group assignment did not predict moderate-to-severe gastroenteritis (odds ratio, 1.06; 95% CI, 0.76 to 1.49; P=0.74). There were no significant differences between the probiotic group and the placebo group in the median duration of diarrhea (52.5 hours [interquartile range, 18.3 to 95.8] and 55.5 hours [interquartile range, 20.2 to 102.3], respectively; P=0.31) or vomiting (17.7 hours [interquartile range, 0 to 58.6] and 18.7 hours [interquartile range, 0 to 51.6], P=0.18), the percentages of participants with unscheduled visits to a health care provider (30.2% and 26.6%; odds ratio, 1.19; 95% CI, 0.87 to 1.62; P=0.27), and the percentage of participants who reported an adverse event (34.8% and 38.7%; odds ratio, 0.83; 95% CI, 0.62 to 1.11; P=0.21).
CONCLUSIONS: In children who presented to the emergency department with gastroenteritis, twice-daily administration of a combined L. rhamnosus–L. helveticus probiotic did not prevent the development of moderate-to-severe gastroenteritis within 14 days after enrollment. (Funded by the Canadian Institutes of Health Research and others; PROGUT number, NCT01853124.)

First Authors:
Stephen B Freedman

Correspondence Authors:
Stephen B Freedman

All Authors:
Stephen B Freedman,Sarah Williamson‑Urquhart,Ken J Farion,Serge Gouin,Andrew R Willan,Naveen Poonai,Katrina Hurley,Philip M Sherman,Yaron Finkelstein,Bonita E Lee,Xiao‑Li Pang,Linda Chui,David Schnadower,Jianling Xie,Marc Gorelick,Suzanne Schuh