Multi-DOSE Oral Ondansetron for Pediatric Acute GastroEnteritis (DOSE-AGE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03851835|
Recruitment Status : Recruiting
First Posted : February 22, 2019
Last Update Posted : September 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Gastroenteritis Viral Illness Vomiting Diarrhea||Drug: Ondansetron Oral Solution Drug: Oral Placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1030 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Multi-dose Oral Ondansetron For Pediatric Gastroenteritis: A Pragmatic Randomized Controlled Trial|
|Actual Study Start Date :||September 4, 2019|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||June 2023|
Experimental: Ondansetron Oral Solution
Ondansetron Oral Solution (4mg/5mL solution) - Dose = 0.15mg/kg. One dose every 8 hours (q8h). Six doses over 48 hours.
Drug: Ondansetron Oral Solution
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).
Other Name: Zofran
Placebo Comparator: Placebo Oral Solution
Compounded Placebo Oral Solution to match experimental arm
Drug: Oral Placebo
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).
- 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. [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]
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)
- Vomiting Duration [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]Number of hours of vomiting following ED disposition.
- Vomiting Frequency [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]Number of episodes of vomiting following ED disposition.
- Vomiting Proportion [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]The proportion who experience vomiting following ED disposition.
- Proportion of participants who require an unscheduled health care visit [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]Unscheduled health care provider visits following Emergency Department disposition. Is there a difference in the proportion who require an unscheduled health care provider visit following ED disposition.
- Proportion of participants who require Intravenous (IV) Rehydration [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]Is there a difference in the proportion who require intravenous rehydration following ED disposition.
- Satisfaction with care: 5 point Likert Scale [ Time Frame: 168 hours after baseline ]
Caregivers will be asked about their level of satisfaction with the therapy provided measured on the following 5 point Likert scale (choose one option):
- 1 - Very dissatisfied
- 2 - Dissatisfied
- 3 - Neither satisfied, nor dissatisfied
- 4 - Satisfied
- 5 - Very Satisfied
- Safety Profile of Multiple Doses of Oral Ondansetron [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]To determine if the discharge of children with AGE associated vomiting who are administered ondansetron in the ED with additional doses to be taken at home is associated with adverse events (e.g. diarrhea, revisits) as compared with placebo.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03851835
|Contact: Sarah Williamson-Urquhartfirstname.lastname@example.org|
|Contact: Stephen Freedman, MDemail@example.com|
|Alberta Children's Hospital||Recruiting|
|Calgary, Alberta, Canada, T3B 6A8|
|Contact: Sarah Williamson-Urquhart 403-955-2482 firstname.lastname@example.org|
|Principal Investigator: Stephen Freedman, MD|
|Sub-Investigator: Graham Thompson, MD|
|Sub-Investigator: Antonia Stang, MD|
|Stollery Children's Hospital||Recruiting|
|Edmonton, Alberta, Canada, T6G 2C8|
|Contact: Manasi Rajagopal 780-248-5440 email@example.com|
|Principal Investigator: Andrew Dixon, MD|
|Children's Hospital of Winnipeg||Recruiting|
|Winnipeg, Manitoba, Canada, R3A 1S1|
|Contact: Jeannine Schellenberg 204-789-3206 JSchellenberg@chrim.ca|
|Principal Investigator: Darcy Beer, MD|
|Sub-Investigator: Scott Sawyer, MD|
|Children's Hospital London Health Sciences Centre||Recruiting|
|London, Ontario, Canada, N6A 5W9|
|Contact: Leslie Boisvert 519-685-8500 ext 56174 Leslie.Boisvert@lhsc.on.ca|
|Contact: Kamary CoriolanoDaSilva 519-685-8500 ext 56174 Kamary.CoriolanoDaSilva@lhsc.on.ca|
|Principal Investigator: Gary Joubert, MD|
|Children's Hospital of Eastern Ontario (CHEO)||Active, not recruiting|
|Ottawa, Ontario, Canada, K1H 8L1|
|Centre Hospitalier Universitaire Sainte Justine||Active, not recruiting|
|Montreal, Quebec, Canada, HT3 1C5|
|Principal Investigator:||Stephen Freedman, MD||University of Calgary|