What is the evidence.
See evidence matrix  in Epistemonikos later

We found three systematic reviews [1],[2],[3] including nine randomized controlled trials, reported in eight references [4],[5],[6],[7],[8],[9],[10],[11] (one reference reports two studies [10]).

What types of patients were included

All trials included exclusively pediatric patients, between 3 to 71 months old, with acute diarrhea of viral or bacterial etiology. Four studies considered only inpatients [4],[5],[8],[10] and five outpatients only [6],[7],[9],[10],[11]. Stool output and number of diarrheic stools the day before inclusion was registered, showing no difference between racecadotril and placebo groups. 

What types of interventions were included

Trials evaluated oral racecadotril; in six the dose was 1.5 mg/kg every 8 hours [4],[5],[6],[7],[8],[9],  two administered 10 mg or 20 mg every 8 hours adjusted by body weight (over or under 9 kg) and one did not specify dosage [11].  

What types of outcomes
were measured

Proportion of responders (defined as diarrhea duration less than 48 hours), proportion of patients not cured at fifth day of therapy, daily stool output and volume and number of vomits the first 48 hours of treatment. 

To whom this evidence does and does not apply

• This evidence applies to pediatric patients with clinical diagnosis of acute diarrhea of viral or bacterial etiology, hospitalized or in ambulatory care. 
• This evidence does not apply to immunosuppressed patients or with severe comorbidities.

• We selected “proportion of responders” as outcome because it was the only outcome critical for decision-making according to the opinion of the authors of this summary. It was also the only one included in all randomized trials available and was subject of analysis of one of the reviews [3] included in this summary.
• It might be relevant to analyze outcomes as need for hospitalization, need for intravenous hydration, additional emergency department visits, among others.

• None of the studies reported significant adverse effects with racecadotril. It is also an approved therapy for pediatric population [12].
• The certainty of the evidence is moderate, but there is a probable benefit of the intervention in terms of decreasing diarrhea duration and it would be also a low risk therapy.

• Racecadotril is a complement to acute diarrhea treatment and does not replace the use of oral rehydration solutions.
• Pediatric practice involves parents and/or patient caregivers. It is important to consider their concerns about disease. In this scenario and highlighting acute diarrhea is usually a self-limited condition, it is reasonable to suggest racecadotril as an adjuvant therapy that may have benefits but involves costs.

• Racecadotril is still not widely available and adds costs to standard treatment for acute diarrhea (oral rehydration solution). Considering it could shorten the duration of the disease which might lower risk of dehydration, using racecadotril could decrease healthcare costs (hospital bed use, emergency department visits). However, it is not possible to make an appropriate cost-benefit analysis with the evidence available, especially because of the lack of information on other important outcomes. 

Differences between this summary and other sources

• Our summary is consistent with the systematic reviews identified.
•  We reviewed the Evidence-Based Guidelines for the Management of Acute Gastroenteritis in Children of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and the European Society for Pediatric Infectious Diseases [13]. Their recommendations are consistent with the conclusions of our summary.

• The certainty of the available evidence is moderate, although only one outcome was analyzed.
• We are aware of ongoing randomized controlled trials about racecadotril for acute diarrhea in children, so it is possible that they provide new information for this question in the future.