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

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ClinicalTrials.gov Identifier: NCT03851835
Recruitment Status : Not yet recruiting
First Posted : February 22, 2019
Last Update Posted : August 9, 2019
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Women and Children's Health Research Institute (WCHRI)
The Hospital for Sick Children
Children's Hospital Research Institute of Manitoba
University of Manitoba
Université de Montréal
University of Ottawa
University of Alberta
Alberta Children's Hospital Research Institute
University of Western Ontario, Canada
Information provided by (Responsible Party):
University of Calgary

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.

Condition or disease Intervention/treatment Phase
Acute Gastroenteritis Viral Illness Vomiting Diarrhea Drug: Ondansetron Oral Solution Drug: Oral Placebo Phase 3

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1030 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-dose Oral Ondansetron For Pediatric Gastroenteritis: A Pragmatic Randomized Controlled Trial
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).




Primary Outcome Measures :
  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. [ 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)


Secondary Outcome Measures :
  1. Vomiting Duration [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]
    Number of hours of vomiting following ED disposition.

  2. Vomiting Frequency [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]
    Number of episodes of vomiting following ED disposition.

  3. Vomiting Proportion [ Time Frame: Measured 24, 48, and 168 hours after baseline visit ]
    The proportion who experience vomiting following ED disposition.

  4. 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.

  5. 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.

  6. 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


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of acute intestinal infectious process (as defined by the protocol) confirmed. by the treating MD.
  • 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Sarah Williamson-Urquhart 403-955-2482 sarah.urquhart@ahs.ca
Contact: Stephen Freedman, MD 403-955-7740 stephen.freedman@ahs.ca

Locations
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Canada, Alberta
Alberta Children's Hospital Not yet recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Sarah Williamson-Urquhart    403-955-2482    sarah.urquhart@ahs.ca   
Principal Investigator: Stephen Freedman, MD         
Sub-Investigator: Graham Thompson, MD         
Sub-Investigator: Antonia Stang, MD         
Stollery Children's Hospital Not yet recruiting
Edmonton, Alberta, Canada, T6G 2C8
Contact: Manasi Rajagopal    780-248-5440    manasi@ualberta.ca   
Contact: Mithra Sivakumar    780-492-0451    mithra@ualberta.ca   
Principal Investigator: Andrew Dixon, MD         
Canada, Manitoba
Children's Hospital of Winnipeg Not yet 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         
Canada, Ontario
Children's Hospital London Health Sciences Centre Not yet recruiting
London, Ontario, Canada, N6A 5W9
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) Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Tremaine Rowe    613-737-7600 ext 3348    trowe@cheo.on.ca   
Contact: Candice McGahern    613-737-7600 ext 4111    cmcgahern@cheo.on.ca   
Principal Investigator: Amy Plint, MD         
Canada, Quebec
Centre Hospitalier Universitaire Sainte Justine Not yet recruiting
Montreal, Quebec, Canada, HT3 1C5
Contact: Marie-Christine Auclair    514-345-4931 ext 3827    marie.christine.auclair@recherche-ste-justine.qc.ca   
Principal Investigator: Serge Gouin, MD         
Sponsors and Collaborators
University of Calgary
Canadian Institutes of Health Research (CIHR)
Women and Children's Health Research Institute (WCHRI)
The Hospital for Sick Children
Children's Hospital Research Institute of Manitoba
University of Manitoba
Université de Montréal
University of Ottawa
University of Alberta
Alberta Children's Hospital Research Institute
University of Western Ontario, Canada
Investigators
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Principal Investigator: Stephen Freedman, MD University of Calgary

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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT03851835     History of Changes
Other Study ID Numbers: OND18-2045
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Calgary:
Vomiting
Zofran
Ondansetron
Gastroenteritis
Pediatrics
DOSE-AGE

Additional relevant MeSH terms:
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Diarrhea
Vomiting
Gastroenteritis
Virus Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Gastrointestinal Diseases
Digestive System Diseases
Pharmaceutical Solutions
Ondansetron
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents