Multi-dose Oral Ondansetron for Pediatric Gastroenteritis: study Protocol for the multi-DOSE oral ondansetron for pediatric Acute GastroEnteritis (DOSE-AGE) pragmatic randomized controlled trial.

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice. METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began recruiting children aged 6 months to 18 years with a minimum of three episodes of vomiting in the 24 h preceding enrollment, <72 h of gastroenteritis symptoms and who were administered a dose of ondansetron during their ED visit. We are recruiting 1030 children (1:1 allocation via an internet-based, third-party, randomization service) to receive a 48-h supply (i.e., six doses) of ondansetron oral solution or placebo, administered on an as-needed basis. All participants, caregivers and outcome assessors will be blinded to group assignment. Outcome data will be collected by surveys administered to caregivers 24, 48 and 168 h following enrollment. The primary outcome is the development of moderate-to-severe gastroenteritis in the 7 days following the ED visit as measured by a validated clinical score (the Modified Vesikari Scale). Secondary outcomes include duration and frequency of vomiting and diarrhea, proportions of children experiencing unscheduled health care visits and intravenous rehydration, caregiver satisfaction with treatment and safety. A preplanned economic evaluation will be conducted alongside the trial. DISCUSSION: Definitive data are lacking to guide the clinical use of post-ED visit multidose ondansetron in children with acute gastroenteritis. Usage is increasing, despite the absence of supportive evidence. The incumbent additional costs associated with use, and potential side effects such as diarrhea and repeat visits, create an urgent need to evaluate the effect and safety of multiple doses of ondansetron in children focusing on post-emergency department visit and patient-centered outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03851835. Registered on 22 February 2019.

Depressing research.

Suppression of the publication of negative trials of serotonin-selective reuptake inhibitors (SSRI) in children (Apr 24, p 1335) is more than just a matter of "confusion, manipulation, and institutional failure". It is a crime. To blandly illustrate its severity, we can analogise the situation as follows: would you be concerned if a colleague prescribed penicillin to a child who had an uncomplicated upper respiratory tract infection of viral aetiology? Would you be more concerned if you heard that this child had a serious anaphylactic reaction to the penicillin at home? And how much more concerned would you be if you found out that the prescribing doctor was previously aware of the child's severe penicillin allergy? The latter scenario could be deemed malpractice. How, then, is it acceptable for pharmaceutical companies to suppress publication of SSRI studies that showed a lack of efficacy and an increased risk of serious adverse events in the children and adolescents in experimental trial groups (other than for fluoxetine)? Intentional concealment of these data, an accusation for which there is already public evidence, must be considered a form of corporate violence.