A Multicenter Randomized Controlled Trial of a Liquid Loperamide Product Versus Placebo in the Treatment of Acute Diarrhea in Children

Abstract

This randomized, double-blind, placebo-controlled trial of 48 hours' duration conducted in 13 primary care ambulatory practices in the United States and Mexico was used to compare the efficacy and safety of loperamide with placebo for the treatment of acute diarrhea in children aged 2 through 11 years. Two hundred fifty-eight children with acute nonspecific diarrhea were enrolled. Children were randomly assigned to treatment with loperamide HCl 0.5 mg/5 mL (n = 130) or placebo (n = 128). The first dose of loperamide consisted of either 1.0 mg (children 2 through 5 years of age) or 2.0 mg (children 6 through 11 years of age) of study medication under the observation of study personnel. This was followed by 1 mg after each unformed stool, with a total daily dose of up to 3.0 mg in the children 2-5 years of age, 4.0 mg in the children 6-8 years of age, and 6.0 mg in the children 9-11 years of age. The primary outcome measures were time to last unformed stool, time to first unformed stool, number of unformed stools during six consecutive 8-hour periods, and overall rating of efficacy/acceptability. Secondary outcomes included abdominal pain/cramping, vomiting, and fever. Children who received loperamide had significantly shorter time to last unformed stool (p = 0.0017) and fewer numbers of unformed stools (p = 0.0237) than children who received placebo. The end-of-study overall efficacy/acceptability rating of loperamide was significantly better than for placebo (p = 0.0107). All other clinically important outcome measures related to diarrhea relief favored loperamide. There was no significant difference in the incidence of drug-related adverse events between treatment groups, although total adverse events were reported more frequently (p = 0.048) by the loperamide group (15%) compared with the placebo group (7%). In conclusion, this controlled study provides data demonstrating that at recommend doses, loperamide is well tolerated and significantly shortens the duration and severity of symptoms of acute nonspecific diarrhea in children 2 through 11 years of age.

Loperamide Therapy for Acute Diarrhea in Children: Systematic Review and Meta-Analysis

“…Key researchers in the field did not suggest any additional trials. Of the 91 articles examined, we excluded 34 studies with no control group, 16 studies where children younger than 12 y of age were not included, one study where we were unable to determine the number of children younger than 12 y of age, and 24 studies that did not otherwise meet inclusion criteria, leaving 16 studies that met the four inclusion criteria (Figure 1) [16–31]. We excluded one study because only subanalysis results were presented [29].…”

“…While four out of 13 studies defined diarrhea resolution as the time to the last unformed stool [16,17,26,31], four studies defined diarrhea resolution as change in stool consistency [22], <15 g of stool/kg/d [24], two or fewer liquid/soft stools/d [18], or return to normal bowel habits [21], and five studies did not report their criteria for diarrhea resolution [19,20,23,25,27]. …”

ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults

“…Th us, the mechanisms of antidiarrheal eff ect of loperamide are indirect or direct inhibition of mucosal secretion and reduction in motility. In a comparative randomized trial in patients with TD, loperamide reduced the number of diarrheal stools passed when compared with BSS ( 108 ) and loperamide was shown to shorten diarrhea in both children ( 109 ) and adults with acute diarrhea ( 110 ). Th e recommended dose of loperamide for therapy for adults with diarrhea is 4 mg initially followed by 2 mg aft er subsequently Summary of evidence .…”

Traveler's Diarrhea in the Pediatric Population: Etiology and Impact

“…No significant adverse effects were reported, but the group given loperamide had a higher rate of adverse effects, compared with the group given placebo (15% vs. 7%) [22]. An earlier study of a 2-center, placebo-controlled clinical trial conducted in Liverpool, England, and Libya reported no statistically significant differences in the course of gastroenteritis [23].…”