Racecadotril for acute diarrhoea in children

Abstract

Background: Acute diarrhoea is a leading cause of death for children under five years of age. Most deaths are caused by excessive fluid and electrolyte losses. Racecadotril is an anti-secretory drug that has been used for acute diarrhoea in children as an adjunct to oral rehydration therapy.

Objectives: To assess the efficacy and safety of racecadotril for treating acute diarrhoea in children under five years of age.

Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library Issue 3, March 2019); MEDLINE; Embase; LILACS; ClinicalTrials.gov; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), up to 4 March 2019, for clinical trials regardless of publication language or status.

Selection criteria: Randomized controlled trials (RCTs) that compared racecadotril to placebo or no intervention in addition to standard care (oral rehydration therapy) in children under five with acute diarrhoea. The primary outcomes were failure of oral rehydration, duration of diarrhoea, and number of stools. The secondary outcomes were stool output, length of the hospital stay, and adverse events.

Data collection and analysis: Two review authors independently assessed trial eligibility, extracted the data and assessed risk of bias. We presented dichotomous data with risk ratios (RR) and continuous data with mean difference (MD) or standardized mean difference (SMD). Where appropriate, we combined trials with meta-analysis and used a random-effects model if there was significant heterogeneity (I² ≥ 50%). We assessed the certainty of the evidence using the GRADE approach.

Main results: Seven RCTs with a total of 1140 participants met the inclusion criteria. The trials were carried out on children aged three months to five years, in outpatient and inpatient facilities from France, Spain, Peru, India, Kenya, and Ecuador. The efficacy and safety of racecadotril were compared to placebo or no treatment. Racecadotril may reduce the risk of rehydration failure (RR 0.41, 95% CI 0.13 to 1.23; 2 RCTs, 192 participants; low-certainty evidence). Data on duration of diarrhoea, number of stools in the first 48 hours are insufficient to reach a conclusion; stool output in the first 48 hours appears to be lower in the two trials measuring this, although the data is not combinable. Length of hospital stay was similar in two studies measuring this, and overall there was no evidence that racecadotril increased overall rate of adverse events (RR 0.90, 95% CI 0.66 to 1.22; 5 RCTs, 688 participants; low-certainty evidence). Most adverse events in the racecadotril group were mild or moderate.

Authors' conclusions: Racecadotril seems to be a safe drug but has little benefit in improving acute diarrhoea in children under five years of age. Current evidence does not support routine use of racecadotril in management of acute diarrhoea in children under five outside of the context of placebo controlled RCTs. 18 December 2019 Up to date All studies incorporated from most recent search All studies identified during the most recent search (4 Mar, 2019) have been incorporated in the review, and no ongoing studies identified.