Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial

Abstract

BackgroundVomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking.ObjectivesTo compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT.Methods/DesignMulticentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled.DiscussionThe trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results.Trial RegistrationClinicalTrials.gov: NCT01257672

Oral Ondansetron versus Domperidone for Acute Gastroenteritis in Pediatric Emergency Departments: Multicenter Double Blind Randomized Controlled Trial

“…The protocol (S1 Protocol), which has been previously published [24], obtained the ethical approval by the Independent Bioethic Committee of the coordinating center (IRCCS Burlo Garofolo, Trieste Italy) on November 8, 2010 (Approval Number: S-115) and, subsequently, by the ethic committees of each participating center (Comitato Etico dell’Azienda Ospedaliera Spedali Civili di Brescia; Comitato Etico della Provincia di Modena; Comitato Etico per la sperimentazione dell’Azienda Ospedaliera Istituti Ospitalieri di Verona; Comitato Etico per la sperimentazione clinica della Provincia di Treviso; Comitato Etico dell’Azienda Ospedaliera Universitaria Maggiore della Carità di Novara; Comitato Etico della AUSL di Bologna; Comitato Etico locale per la sperimentazione dei farmaci dell’A.O. Universitaria Anna Meyer, Firenze; Comitato Etico interzonale della ASUR Zona Territoriale 8 di Civitanova Marche e Zona Territoriale 9 di Macerata; Comitato Etico per la sperimentazione clinica dell’IRCCS Ospedale pediatrico Bambino Gesù di Roma; Comitato Etico dell’IRCCS Istituto Giannina Gaslini, Genova; Comitato Etico dell’Azienda Ospedaliera OIRM S. Anna di Torino; Comitato Etico di Area Vasta Romagna di Cesena e Istituto scientifico romagnolo per lo studio e la cura dei tumori di Meldola, Forlì; Comitato Etico dell’Azienda Ospedaliera S. Giuseppe Moscati di Avellino; Comitato Etico per la sperimentazione dell’Azienda Ospedaliera di Padova).…”

“…According to the published protocol [24], the primary outcome was the percentage of patients who were administered nasogastric or intravenous rehydration after symptomatic oral treatment failure, defined as vomiting or fluid refusal after the second ORT attempt. Secondary outcomes were: a) the percentage of subjects remaining in ED for observation stay for more than 6 hours; b) the percentage of subjects requiring hospital admission during the ED stay; c) subjects with episodes of vomiting and number of episodes in the 3 treatment groups during the ED stay and during the 48-hour follow-up period; d) the percentage of subjects presenting adverse events during ED stay and during the 48-hour follow-up period.…”

Randomized Study of Ondansetron Versus Domperidone in the Treatment of Children With Acute Gastroenteritis

“…Most of the patients will recover from their symptoms within 72 hours after the start of treatment. Further studies including a large multi-center randomized controlled trial [20] that is currently being implemented will hopefully provide answers to some of the specific questions regarding the possible role of ondansetron in children with AGE.…”

Análisis de costo efectividad de ondansetrón para el tratamiento del vómito en niños menores de cinco años con gastroenteritis en Colombia

“…Actualmente un estudio que compara ondansetrón y domperidona se encuentra en curso, y según resultados podría considerarse la necesidad de reevaluar las recomendaciones sobre cuál antiemético utilizar [25]. A la fecha, ondansetrón es el antiemético con mayor evidencia de efectividad, perfil de seguridad, y costo-efectividad para controlar el vómito en niños con gastroenteritis, evitar hidratación endovenosa y la hospitalización por esta causa.…”