Table 9 Summary of the characteristics and results of six randomized, controlled trials included in the review

Canani et al., 2007 (Italy)

Prospective, multicenter, single-blind, randomized, controlled

1 × 10⁹ CFU of Bacillus clausii bid for 5 days + ORS for 3–6 h vs ORS for 3 to 6 h (followed by full strength formula of lactose or cows’ milk, depending on age, in both groups)

Total duration of diarrhea, number of stools/day and their consistency, incidence and median duration of vomiting, fever (> 37.5 °C), number of hospital admissions, safety and tolerability

Median duration of diarrhea in patients receiving Bacillus clausii (118 h) similar to control group (115 h), with an estimated difference of 1 h between both groups (p = 0.76). All other outcomes were also similar in both groups. B. clausii was well tolerated, with no observed adverse events.

Lahiri, 2008 (India)

Phase III, controlled, open-label, randomized, parallel-group, multicenter, comparative

2 × 10⁹ CFU of B. clausii bid + ORS + 20 mg/day of zinc supplement, for 5 days vs ORS + 20 mg/day of zinc supplement, for 5 days

Duration of diarrhea, mean number of daily stools, effect on consistency of stools, vomiting episodes per day, reported adverse events, parents’ overall global assessment of tolerability at end of treatment period

Mean (SD) duration of diarrhea lower in the experimental group (48.6 [38.2] h) vs control group (56.1 [40] h; p = 0.13). Difference in the mean (SD) number of stools until recovery statistically not significant (p = 0.19); trend favoring the experimental group (7.4 [6.5] motions vs 8.6 [6.5] motions in control group).

Lahiri, Jadhav et al., 2015 (India)

Open-label, prospective, randomized, controlled

2 × 10⁹ CFU of B. clausii bid + ORS + zinc, for 5 days vs ORS + zinc for 5 days

Mean duration of diarrhea, mean duration of hospitalization, frequency of diarrhea, direct and indirect costs

Mean duration of diarrhea 22.64 h and mean duration of hospital stay 2.78 days in the B. clausii group vs 47.05 h and 4.30 days, respectively, in the control group (p < 0.01 for diarrhea duration). Treatment with B. clausii reduced total treatment costs by 472 Indian rupees compared to ORS alone.

Lahiri, D’Souza et al., 2015 (India)

Open-label, prospective, randomized, controlled

2 × 10⁹ CFU of B. clausii bid + ORS + zinc, for 5 days vs ORS + zinc for 5 days

Mean duration of diarrhea, mean stool frequency, % of children with no dehydration, % of children benefiting from breastfeeding

Mean (SD) duration of diarrhea 22.26 h and mean stool frequency 1.15 in the B. clausii group vs 34.16 h and 1.70, respectively in control group (p < 0.05).

Maugo, 2012 (Kenya)

Randomized, double-blind, placebo- controlled

2 × 10⁹ CFU of B. clausii bid + ORS + zinc sulfate, for 5 days vs zinc sulfate + ORS + 1 vial bid of a placebo packaged in identical looking vials containing sterile water, for 5 days

Mean duration of diarrhea, mean duration of hospitalization, mean reduction of the number of diarrheal episodes per day

Mean (SD) duration of diarrhea in B. clausii group was shorter (77.59 [34.10] h) than placebo group (86.74 [40.16] h), with mean absolute difference between groups of 9.15 h (p = 0.248). Significant decrease in mean number of diarrheal motions on day 3 (2.74 [1.81] motions) in the B. clausii group vs 3.80 [2.70] motions in placebo group, mean absolute difference = 1.05 motions; p = 0.033) and day 4 (1.45 [1.13] motions in the B. clausii group vs 2.35 [2.19] motions in placebo group, mean absolute difference = 0.9 motions; p = 0.018) in the B. clausii group vs placebo group.

Urtula, Dacula, 2008 (The Philippines)

Monocentric, randomized, controlled

2 × 10⁹ or 4 × 10⁹ CFU of B. clausii per day, depending on the age of the children + ORS, for 3 days vs ORS for 3 days

Mean duration of diarrhea, mean duration of hospitalization, mean frequency of stools

Mean (SD) duration of diarrhea significantly shorter in the B. clausii group (69.84 [16.84] h) than in control group (83.76 [22.05) h] (p = 0.005), with absolute difference of duration of diarrhea between groups of 13.92 h. Mean duration of hospital stay was also shorter favoring B. clausii group (59.0 h vs 76.8 h) (p = 0.063).