Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.
Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.
In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by, of Cincinnati (Ohio) Children’s Hospital Medical Center.
Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.
However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.
“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published.
Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).
Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.
In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.
That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.
As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.
Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.
Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.
Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.
Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”
The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.
The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.
SOURCES: Schnadower D et al. ; Freedman SB et al. .