Lower dose zinc for childhood diarrhea: a randomized, multicenter trial

BACKGROUND: The WHO recommends 20 mg/day of supplemental zinc for children with acute diarrhea for 10-14 days; in previous trials this dosage improved diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children ages 6 to 59 months in India and Tanzania with acute diarrhea to one of three arms (5, 10 or 20 mg zinc sulfate for 14 days). The three primary outcomes were diarrhea duration >5 days and mean number of stools (tested for non-inferiority), and vomiting within 30 minutes of zinc administration (tested for superiority). RESULTS: The proportion of children with diarrhea duration >5 days was 6.5%, 7.7%, 7.2% in the 20 mg, 10 mg and 5 mg groups, respectively. The difference between 20 mg and 10 mg dosages was 1.2% (upper bound of one-sided 98.75% CI 3.6%) and between 20 mg and 5 mg was 0.7% (upper bound 3.0%), both below the 4% noninferiority margin (4%). The mean number of loose stools was 10.7, 10.9, and 10.8 in the 20 mg, 10 mg and 5 mg groups, respectively. The differences between 20 mg and 10 mg groups was 0.3 (upper bound 1.1), and between 20 mg and 5 mg group, 0.1 (upper bound 0.9), both below the noninferiority margin (2 stools). Vomiting within 30 minutes of zinc administration occurred in 19.3%, 15.6%, 13.7%, respectively, and was significantly lower in the 10 mg (relative risk 0.81, 97.5% CI 0.67 to 0.96) and 5 mg (0.71, 97.5% CI 0.59 to 0.86) groups. Both dosages also reduced vomiting after 30 minutes of dosing. CONCLUSION: Compared with the standard 20 mg dosage of zinc, lower dosages had noninferior efficacy for diarrhea and reduced vomiting in children with diarrhea. NCT03078842.