Multi-dose Oral Ondansetron for Pedatric Gastroenteritis: A Randomized Controlled Trial
Status: not yet recruiting
ClinicalTrials.gov Identifier: NCT03851835
Principal Investigator: Stephen Freedman
Project Manager: Sarah Williamson-Urquhart
To determine if treatment of infants presenting with bronchiolitis to the emergency department (ED) with nebulized epinephrine and a 2-day course of oral dexamethasone is effective in reducing the need for hospitalization (due to bronchiolitis) by day 7 compared to placebo.
To determine if treatment of infants presenting with bronchiolitis to the ED with nebulized epinephrine and a 2-day course of oral dexamethasone is effective in reducing hospitalizations (for bronchiolitis) at enrolment ED visit and/or by day 21 compared to placebo.
To determine if there is a difference between groups in all cause hospitalizations by day 7, all cause hospitalizations by day 21, all cause ED visits over 21 days, length of ED visit, length of hospitalization, length of symptoms, and health care-related costs.
We will enroll 1800 infants across Canada at participating sites. We will enroll children > 60 days of age and < 12 months of age presenting with bronchiolitis during the winter viral season. Children born at less than 37-weeks gestation and less than 60 days corrected age and those with known chronic lung disease, congenital heart disease, immunodeficiency, recent exposure to varicella, and those who are critically unwell will not be enrolled in the study.
To be eligible to participate in the study, individuals must meet all of the following criteria:
1. Provision of signed and dated informed consent and assent (where applicable) forms
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Diagnosis of acute intestinal infectious process confirmed by the treating ED physician: The diagnosis of gastroenteritis/acute intestinal infectious process is at the discretion of the emergency department supervising physician. Alternative terminologies that reflect a similar diagnosis are acceptable provided they meet all other eligibility criteria. Examples include: viral illness, diarrhea, vomiting, upper respiratory infection, post-infectious gastroenteritis, antibiotic associated diarrhea, toddlers diarrhea, viral infection, enteritis, viremia, fever, and bronchiolitis.
4. Child/youth aged 6 months to 17.99 years.
5. Presence of ≥ 3 episodes of vomiting in the preceding 24 hour period (in the 24 hours preceding the screening process performed by the research team).
6. Duration of vomiting and/or diarrheal symptoms < 72 hours (a 24 hour vomit and diarrhea free interval denotes a separate illness and only continuous days since the last 24 hour vomit and diarrhea free period are included).
7. A minimum of 1 episode of vomiting within 6 hours of the screening process performed by the research team (time of approach and screening to be recorded): Date of time of assessment of eligibility for this study.
8. A minimum of 1 dose of ondansetron (oral or intravenous) provided during the current emergency department visit.
Individuals who meet any of the following criteria will be excluded from participation in this study:
1. Bilious (having a green or bright yellow colour, indicating larger amounts of bile in the stomach) or bloody vomit during current illness: This may indicate an alternate diagnosis.
2. Known hypersensitivity to ondansetron or any serotonin receptor antagonist (e.g. palonosetron, dolasetron, granisetron).
3. Known allergic reaction to components of ondansetron (citric acid, sodium benzoate, sodium citrate dihydrate, and strawberry flavor, sorbitol)27 or the placebo medication (methylparaben, glycerin, citric acid, potassium sorbate, sorbitol, strawberry flavor)
4. History or family history (first degree relative) of prolonged QT syndrome
5. Presence of complex congenital heart disease
6. History or family history (first degree relative) of cardiac arrhythmia
7. Concomitant use (within the past 48 hours) of any of the following – For a full list of possible medications in the following categories, please references the TMOP:
a) QTc prolonging medications27 (e.g. methadone, anti-depressants, antiarrhythmics)
b) Medications known to cause torsades de pointes27 (e.g. macrolide antibiotics, apo morphine (a morphine decomposition product that does not contain morphine or it’s skeleton, nor does it bind to opioid receptors; acts as an antagonist of 5-HT2 and α-adrenergic receptors with high affinity37
c) Medications that cause electrolyte abnormalities27 (e.g. high dose corticosteroids, diuretics)
d) Serotonergic or neuroleptic medications: Risk of serotonin syndrome or neuroleptic malignant syndrome27 (e.g. triptans, SSRIs, SNRIs, fentanyl, MAOIs, lithium)
e) Any 5-HT3 receptor antagonist excluding ondansetron: Cross reactivity has been reported between different 5-HT3 antagonists27
8. Unable to complete follow-up due to travel, no telephone or internet availability, or a language barrier beyond reasonable accommodation.
9. Previously enrolled in this study.