Multi-DOSE Oral Ondansetron for Pediatric Acute GastroEnteritis

NCT03851835 | Completed Phase 3 DMC

• 1 other identifier: OND18-2045
• Study Type: interventional
• Target: 1,030
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Acute Gastroenteritis; Viral Illness; Vomiting; Diarrhea

Keywords

Vomiting; Zofran; Ondansetron; Gastroenteritis; Pediatrics; DOSE-AGE

Outcome Measures

Primary Outcomes (1)

• Development of moderate to severe disease as defined by the Modified Vesikari Scale (MVS) Score of ≥ 9 following ED evaluation - change in the MVS score between Hour 0 and Hour 168 of the study.

  The Modified Vesikari Scale Score (MVS) is a composite measure which includes several variables representing the severity of disease - points are summed to provide an overall score: * Duration of diarrhea (hours): 0 (0 points), 1-96 (1 point), 97-120 (2 points), ≥121 (3 points) * Maximum number of watery stools per 24 hour period: 0 (0 points), 1-3 (1 point), 4-5 (2 points), ≥6 (3 points) * Duration of vomiting (hours): 0 (0 points), 1-24 (1 point), 25-48 (2 points), ≥49 (3 points) * Maximum number of vomiting episodes per 24 hour period: none (0 points), 1 (1 point), 2-3 (2 points), ≥5 (3 points). * Maximum recorded rectal temperature (degrees Celsius): \<37.0 (0 points), 37.1-38.4 (1 point), 38.5-38.9 (2 points), ≥39.0 (3 points) * Unscheduled health care visit: None (0 points), Primary Care (2 points), emergency department (3 points) * Treatment: None (0 points), Rehydration with IV fluids (1 point), Hospitalization (2 points)

  Measured 24, 48, and 168 hours after baseline visit

Secondary Outcomes (6)

• Vomiting Duration

  Measured 24, 48, and 168 hours after baseline visit

• Vomiting Frequency

  Measured 24, 48, and 168 hours after baseline visit

• Vomiting Proportion

  Measured 24, 48, and 168 hours after baseline visit

• Proportion of participants who require an unscheduled health care visit

  Measured 24, 48, and 168 hours after baseline visit

• Proportion of participants who require Intravenous (IV) Rehydration

  Measured 24, 48, and 168 hours after baseline visit

Other Outcomes (1)

• Safety Profile of Multiple Doses of Oral Ondansetron

  Measured 24, 48, and 168 hours after baseline visit

Study Arms (2)

Ondansetron Oral Solution

EXPERIMENTAL

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.

Drug: Ondansetron Oral Solution

Placebo Oral Solution

PLACEBO COMPARATOR

Compounded Placebo Oral Solution to match experimental arm

Drug: Oral Placebo

Interventions

Ondansetron Oral Solution DRUG

Six doses of oral ondansetron (0.15mg/kg) to be administered q8h (every 8 hours) to a maximum of 3 times in a 24 hour period, are provided to the participant/caregiver for use after emergency department disposition (i.e. home use), as needed.

Also known as: Zofran

Ondansetron Oral Solution

Oral Placebo DRUG

Six doses of oral placebo (0.15mg/kg) to be administered q8h (every 8 hours) to a maximum of 3 times in a 24-hour period, are provided to the participant/caregiver for use after emergency department disposition (i.e. home use), as needed.

Placebo Oral Solution

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Calgary: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Women and Children's Health Research Institute (WCHRI): collaborator
• The Hospital for Sick Children: collaborator
• Children's Hospital Research Institute of Manitoba: collaborator
• University of Manitoba: collaborator
• Université de Montréal: collaborator
• University of Ottawa: collaborator
• University of Alberta: collaborator
• Alberta Children's Hospital Research Institute: collaborator
• Western University, Canada: collaborator

Study Sites (6)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2C8, Canada

Location

Children's Hospital of Winnipeg

Winnipeg, Manitoba, R3A 1S1, Canada

Location

Children's Hospital London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario (CHEO)

Ottawa, Ontario, K1H 8L1, Canada

Location

Centre Hospitalier Universitaire Sainte Justine

Montreal, Quebec, HT3 1C5, Canada

Location

Related Publications (3)

• Freedman SB, Williamson-Urquhart S, Plint AC, Dixon A, Beer D, Joubert G, Pechlivanoglou P, Finkelstein Y, Heath A, Zhang JZ, Wallace A, Offringa M, Klassen TP; Pediatric Emergency Research Canada Innovative Clinical Trials Study Group. Multidose Ondansetron after Emergency Visits in Children with Gastroenteritis. N Engl J Med. 2025 Jul 17;393(3):255-266. doi: 10.1056/NEJMoa2503596.

  PMID: 40673584 DERIVED

• Heath A, Rios JD, Williamson-Urquhart S, Pechlivanoglou P, Offringa M, McCabe C, Hopkin G, Plint AC, Dixon A, Beer D, Gouin S, Joubert G, Klassen TP, Freedman SB; PERC-KIDSCAN DOSE-AGE Study Group. A pragmatic randomized controlled trial of multi-dose oral ondansetron for pediatric gastroenteritis (the DOSE-AGE study): statistical analysis plan. Trials. 2020 Aug 24;21(1):735. doi: 10.1186/s13063-020-04651-1.

  PMID: 32838813 DERIVED

• Freedman SB, Williamson-Urquhart S, Heath A, Pechlivanoglou P, Hopkin G, Gouin S, Plint AC, Dixon A, Beer D, Joubert G, McCabe C, Finkelstein Y, Klassen TP; KidsCAN-Pediatric Emergency Research Canada (PERC) Innovative Pediatric Clinical Trials DOSE-AGE Study Group. 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. Trials. 2020 May 27;21(1):435. doi: 10.1186/s13063-020-04347-6.

  PMID: 32460879 DERIVED

MeSH Terms

Conditions

Virus Diseases; Vomiting; Diarrhea; Gastroenteritis

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Stephen Freedman, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 22, 2019
• Study Start: September 14, 2019
• Primary Completion: June 27, 2024
• Study Completion: July 6, 2024
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

CA (6)