A Double-blind, Randomized, Placebo-controlled Trial of Lactobacillus acidophilus for the Treatment of Acute Watery Diarrhea in Vietnamese Children

Abstract

Background: Probiotics are the most frequently prescribed treatment for children hospitalized with diarrhea in Vietnam. We were uncertain of the benefits of probiotics for the treatment of acute watery diarrhea in Vietnamese children.

Methods: We conducted a double-blind, placebo-controlled, randomized trial of children hospitalized with acute watery diarrhea in Vietnam. Children meeting the inclusion criteria (acute watery diarrhea) were randomized to receive either 2 daily oral doses of 2 × 10 CFUs of a local probiotic containing Lactobacillus acidophilus or placebo for 5 days as an adjunct to standard of care. The primary end point was time from the first dose of study medication to the start of the first 24-hour period without diarrhea. Secondary outcomes included the total duration of diarrhea and hospitalization, daily stool frequency, treatment failure, daily fecal concentrations of rotavirus and norovirus, and Lactobacillus colonization.

Results: One hundred and fifty children were randomized into each study group. The median time from the first dose of study medication to the start of the first 24-hour diarrhea-free period was 43 hours (interquartile range, 15-66 hours) in the placebo group and 35 hours (interquartile range, 20-68 hours) in the probiotic group (acceleration factor 1.09 [95% confidence interval, 0.78-1.51]; P = 0.62). There was also no evidence that probiotic treatment was efficacious in any of the predefined subgroups nor significantly associated with any secondary end point.

Conclusions: This was a large double-blind, placebo-controlled trial in which the probiotic underwent longitudinal quality control. We found under these conditions that L. acidophilus was not beneficial in treating children with acute watery diarrhea.

Figure 1

Consort flow diagram for trial screening and randomization

Figure 2

Kaplan-Meier curve of the primary outcome by treatment group Curves showing the probability of still having diarrhea, i.e. the probability of not yet having reached the onset of the first 24-hour diarrhea-free period (y-axis), against the time since randomization (x-axis) by treatment arm in the intention-to-treat population. L. acidophilus (broken line) and placebo (solid line).

Figure 3

Longitudinal viral load measurements of rotavirus by treatment group Plots show rotavirus viral load measurements by quantitative PCR in log₁₀ target copies per ml of feces (y-axis) against time since randomization (x-axis) in the two groups. Grey lines refer to individual patient profiles, solid black lines to LOESS scatterplot smoothers. Longitudinal viral load measurements were collected in patients with confirmed rotavirus infection without bacterial co-infection only.