Multi-DOSE Oral Ondansetron for Pediatric Acute GastroEnteritis (DOSE-AGE)

University of Calgary

Status and phase: Completed; Phase 3

Conditions: Vomiting; Acute Gastroenteritis; Diarrhea; Viral Illness

Treatments: Drug: Ondansetron Oral Solution; Drug: Oral Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03851835

OND18-2045

Details and patient eligibility

About

A phase III, double-blind, parallel-design, randomized, placebo-controlled trial to compare multi-dose oral Ondansetron with placebo as treatment for vomiting secondary to acute gastroenteritis (AGE), after Emergency Department discharge.

Full description

The annual burden of acute gastroenteritis in the United States includes 17 million related episodes and 473,832 hospitalizations. Although oral-rehydration therapy is recommended for children with mild-to-moderate dehydration, it has historically been underused with emergency department (ED) clinicians being more likely to choose intravenous over oral rehydration especially when vomiting is a major symptom. In fact, nearly 95% of children undergoing oral rehydration in Canadian EDs present with recent vomiting. To address this issue, the investigators conducted both a landmark clinical trial and a recent meta-analysis that have demonstrated that the ED use of ondansetron, an anti-emetic, leads to reductions in intravenous rehydration and hospitalization and is cost-effective. However, the available data revealed some associations with increased diarrhea and no evidence of benefits associated with ongoing ondansetron use following ED discharge. Despite the lack of available data, the provision of multiple doses of ondansetron for home use has become routine in many EDs across North America. The literature has differing opinions on the topic of ongoing ondansetron use after ED discharge and given the limited evidence supporting its use, the potential side effects and additional cost, there is an urgent need to definitively evaluate the effect of multiple doses of ondansetron in children, focusing on family-centred, post-index visit outcomes.

A phase III, double-blind, parallel-design, randomized, placebo controlled trial to compare multi-dose oral Ondansetron with placebo as treatment for vomiting secondary to acute gastroenteritis (AGE), after Emergency Department discharge will be conducted. Children and youth, age 6 months to 17.99 years will be enrolled at six (6) Canadian Emergency Departments. The total number of participants recruited will be 1030. Participants will be enrolled at six (6) pediatric emergency departments across Canada.

Children who are provided a minimum of one dose of ondansetron as part of their routine clinical care AND meet other eligibility criteria will be randomized to receive an at-home kit with six (6) doses of Ondansetron Hydrochloride Dihydrate Oral Solution (4mg/5mL solution; dosed at 0.15mg/kg to a maximum single dose of 8mg) or equivalent volume in a Placebo Oral Solution to be administered no sooner than 8 hours after the initial clinical dose was provided by the ED physician. Over the subsequent 48 hours, the study intervention will be administered at a rate of 1 dose every 8 hours (q8h) to a maximum of 3 doses a day (in a 24-hour period (TID)) at the caregiver's discretion. Two (2) additional doses will be provided to the caregiver in case the child vomits a dose.

Enrollment: 1,030 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willingness to comply with all study procedures and availability for the duration of the study.
• Diagnosis of acute intestinal infectious process (as defined by the protocol) confirmed. by the treating physician.
• Age 6 months to 17.99 years.
• Presence of ≥ 3 episodes of vomiting in the preceding 24-hour period.
• Duration of vomiting and/or diarrheal symptoms < 72 hours.
• A minimum of 1 episode of vomiting within 6 hours of the screening process performed by the research team.
• A minimum of 1 dose of ondansetron (oral or intravenous) provided during the current emergency department visit.

Exclusion criteria

• Bilious or bloody vomit during current illness.
• Known hypersensitivity to ondansetron or any serotonin receptor antagonist (e.g. palonosetron, dolasetron, granisetron).
• Known allergic reaction to components of ondansetron (citric acid, sodium benzoate, sodium citrate dihydrate, and strawberry flavor, sorbitol) or the placebo medication (methylparaben, glycerin, citric acid, potassium sorbate, sorbitol, strawberry flavor).
• History or family history (first degree relative) of prolonged QT syndrome.
• Presence of complex congenital heart disease.
• History or family history (first degree relative) of cardiac arrhythmia.
• Concomitant use (within the past 48 hours) of any of the following: QTc prolonging medications, medications known to cause torsades de pointes, medications that cause electrolyte abnormalities, serotonergic or neuroleptic medications, or any 5-HT3 receptor antagonist excluding ondansetron.
• Unable to complete follow-up.
• Previously enrolled in this study.
• History or family history of G6PD deficiency.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,030 participants in 2 patient groups, including a placebo group

Ondansetron Oral Solution

Experimental group

Description:

Ondansetron Oral Solution (4mg/5mL solution) - Dose = 0.15mg/kg. One dose every 8 hours (q8h), as needed. Up to a maximum of six doses over 48 hours.

Treatment:

Drug: Ondansetron Oral Solution

Placebo Oral Solution

Placebo Comparator group

Description:

Compounded Placebo Oral Solution to match experimental arm

Treatment:

Drug: Oral Placebo