Ondansetron Administration to Children With Gastroenteritis, Vomiting and SOME Dehydration in EDs in Pakistan

NCT01870648 | Completed Phase 4 DMC

• 1 other identifier: RSO1026396
• Study Type: interventional
• Target: 918
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective is to determine if the administration of a single dose of oral ondansetron (an anti-vomiting medication), compared to placebo, results in a reduction in intravenous (IV) rehydration therapy in children presenting for emergency department care with some dehydration, vomiting and diarrhea in Pakistan. SOME Dehydration is defined as 2 or more of the following signs and symptoms:

• Restlessness, irritability
• Sunken Eyes
• Drinks eagerly, thirsty
• Skin pinch goes back slowly

Conditions

Dehydration; Gastroenteritis; Vomiting; Diarrhea

Keywords

Low-middle income country; Dehydration; Intravenous Rehydration; Pakistan

Outcome Measures

Primary Outcomes (1)

• Intravenous (IV) Rehydration

  IV rehydration is defined as the IV administration of ≥20 ml/kg over 4 hours an isotonic fluid for the purpose of rehydration within 72 hours of randomization. This definition allows for the occurrence of the primary outcome in children who receive maintenance plus replacement of losses and not simply those who receive a fluid bolus. This will not include those who simply receive maintenance fluids (e.g. 4 ml/kg/hr for those weighing \< 10 kg). This will also enable us to exclude children who undergo IV insertion for the purpose of medication administration. IV rehydration is a powerful marker of treatment failure, a decrease in which is likely to impact practice and influence decision makers since it is drastically more expensive that ORT, it is painful and is associated with a greater risk of adverse events.

  within 72 hours of randomization

Secondary Outcomes (8)

• The proportion of children who vomit during the 4 hour observation period

  within 4 hour observation period after randomization

• The frequency of vomiting during the 4 hour observation period

  within 4 hour observation period after randomization

• Hospitalization > 24 hours

  72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment

• Volume of Oral Rehydration Solution (ORS) consumed (ml/kg) during the 4 hour observation period

  within 4 hour observation period after randomization

• Development of "SOME" dehydration during the 72 hours following randomization amongst children who are discharged

  within 72 hours of randomization

Other Outcomes (2)

• Major Side Effects

  72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment

• Semi- and Intensive Care Unit Admission

  72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment

Study Arms (2)

Ondansetron

EXPERIMENTAL

4 mg oral disintegrating tablet of ondansetron Participant weight 8-15 kg = half dose (2mg) Participant weight greater than 15 kg = full dose (4mg)

Drug: Ondansetron

Placebo (sugar pill)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ondansetron DRUG

Eligible children will receive one weight based (0.13 - 0.26 mg/kg) dose of an oral ondansetron disintegrating tablet. Subsequent therapy will be in accordance with World Health Organization guidelines as dictated by the child's hydration status.

Also known as: Zofran

Ondansetron

Placebo DRUG

Eligible children will receive one dose of an oral disintegrating Placebo (sugar pill) tablet. Subsequent therapy will be in accordance with World Health Organization guidelines as dictated by the child's hydration status.

Also known as: Sugar Pill

Placebo (sugar pill)

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 - 59 months (0.5 - 5 years)
• Symptoms consistent with gastroenteritis (must have a \& b)
• episode of nonbilious, nonbloody vomiting within the 4 hours preceding triage The requirement for only 1 vomiting episode is based on prior work which similarly required 1 vomiting episode within 4 hours of triage. The later study reported a 17% absolute reduction in the use of IV rehydration. The vast majority of children seeking care and enrolled in the aforementioned study had a significantly greater number of vomiting episodes in the preceding 24 hour (mean \>9 episodes).29
• Presence of ≥ 1 episode of diarrhea during the illness We require the presence of only 1 diarrheal stool to enhance our probability of enrolling children with enteritis (as opposed to other diagnoses).
• In fact, of the 8 RCTs performed using antiemetics in children with gastroenteritis in developed countries, only 1 even required the presence of any diarrhea as part of the eligibility criteria (and that study required a single diarrheal stool).
• \- Presence of "SOME" dehydration - 2 or more of the following signs: i. Restlessness, irritability; ii. Sunken Eyes; iii.Drinks eagerly, thirsty; iv.Skin pinch goes back slowly

You may not qualify if:

• Weight \<8 kg
• Vomiting or diarrhea for \> 7 days
• Malnutrition: The WHO definition will be employed - weight for height below -3z scores of the median WHO growth standards
• Severe dehydration (WHO criteria) or hypotension defined as a systolic blood pressure \<70 mm Hg in infants 1 month to 12 months, \< 70 mm Hg + (2 x age in years) in children 1-10 years, \< 90 mm Hg in children ≥ 10 years
• Prior abdominal surgery (excluding hernia)
• Bilious or bloody vomitus
• Known hypersensitivity to ondansetron or any serotonin receptor antagonist
• History or family history of prolonged QT syndrome
• Taking apomorphine or any medication that is generally accepted as having a risk of causing torsades de pointes
• Patients previously enrolled in the study
• Follow-up will not be possible

Sponsors & Collaborators

• Dr. Stephen Freedman: lead
• Bill and Melinda Gates Foundation: collaborator
• Thrasher Research Fund: collaborator
• Aga Khan University: collaborator

Study Sites (2)

Aga Khan University Hospital

Karachi, Pakistan

Location

Aga Khan Hospital for Women and Children (AKHWC)

Kharadar, Karachi, Pakistan

Location

Related Publications (1)

• Freedman SB, Soofi SB, Willan AR, Williamson-Urquhart S, Siddiqui E, Xie J, Dawoud F, Bhutta ZA. Oral Ondansetron Administration to Dehydrated Children in Pakistan: A Randomized Clinical Trial. Pediatrics. 2019 Dec;144(6):e20192161. doi: 10.1542/peds.2019-2161. Epub 2019 Nov 6.

  PMID: 31694979 DERIVED

MeSH Terms

Conditions

Dehydration; Gastroenteritis; Vomiting; Diarrhea

Interventions

Ondansetron; Sugars

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms

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; Carbohydrates

Study Officials

• Stephen Freedman, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Zulfiqar Bhutta, MD

  Aga Khan University - World Health Organization

  PRINCIPAL INVESTIGATOR

• Sajid B Soofi, MD

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics; Alberta Children's Hospital Foundation Professor in Child Health and Wellness Alberta Children's Hospital Theme Lead

Study Record Dates

• First Submitted: May 30, 2013
• First Posted: June 6, 2013
• Study Start: May 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 2, 2018

Record last verified: 2018-02

Locations

PA (2)