Ondansetron Administration to WELL Children With Gastroenteritis Associated Vomiting in EDs in Pakistan
Information source: University of Calgary
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Dehydration; Gastroenteritis; Vomiting; Diarrhea
Intervention: Ondansetron (Drug); Placebo (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Sarah Williamson Official(s) and/or principal investigator(s): Stephen Freedman, MD, Principal Investigator, Affiliation: University of Calgary Zulfiqar Bhutta, MD, Principal Investigator, Affiliation: Aga Khan University - World Health Organization Sajid B Soofi, MD, Principal Investigator, Affiliation: Aga Khan University
Overall contact: Stephen Freedman, MD, Phone: (403)955-7740, Email: stephen.freedman@albertahealthservices.ca
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 vomiting and diarrhea in Pakistan.
Clinical Details
Official title: Ondansetron Administration to WELL Children With Gastroenteritis Associated Vomiting in Emergency Departments in Pakistan
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Intravenous (IV) Rehydration
Secondary outcome: The proportion of children who vomit during the 4 hour observation periodThe frequency of vomiting during the 4 hour observation period Hospitalization > 24 hours Volume of Oral Rehydration Solution (ORS) consumed (ml/kg) during the 4 hour observation period Development of "SOME" dehydration during the 72 hours following randomization amongst children who are discharged Number of diarrheal stools during the 72 hours following randomization Treatment failure Response based on infectious etiology (i.e. bacterial vs. viral), duration of illness (i.e. < 48 vs. ≥ 48 hours), and age (< 18 months vs. ≥ 18 months)
Detailed description:
Gastroenteritis remains one of the most common causes of morbidity and mortality in children
<5 years of age worldwide. A critical factor in the reduction in mortality over the past 30
years has been the introduction of oral rehydration therapy (ORT) for the treatment of
dehydration.
However, its use has stagnated in many low- and middle-income countries (LMIC) where many
children lack access to alternatives such as intravenous (IV) rehydration. When such
children have fluid losses that cannot be replaced orally due to intractable vomiting, death
is common. Finding a safe, non-invasive, and effective strategy to reduce vomiting in
children would substantially decrease the need for IV rehydration and hence morbidity and
mortality in LMICs. Although antiemetic agents are included in the WHO list of Essential
Medicines, their use in children with gastroenteritis is not endorsed by the World Health
Organization (WHO). Concerns include a lack of evidence that antiemetic agents can improve
outcomes and that they are associated with dangerous side effects. However, in high-income
settings, studies on ondansetron, an antiemetic agent, have demonstrated that it can reduce
vomiting, IV rehydration, and hospitalization. Recent reviews by prominent organizations
(e. g. International child Health Review Collaboration; the Committee on the Selection and
Use of Essential Medicines) have indicated an interest in ondansetron use in children with
gastroenteritis, and they have concluded that further evidence is required. This trial aims
to determine if the administration of a single dose of oral ondansetron results in improved
outcomes in children brought for emergency department care with vomiting and diarrhea in
Pakistan.
Two trials will be conducted under the umbrella of one study. The proposed trials will be
identical with the exception of the severity of dehydration at enrollment (either "some" or
none "well").
This study will have immediate impact on patient management. Based on the results, it will
be discovered if oral ondansetron plays a role in reducing the need for intravenous
rehydration in children with gastroenteritis in Pakistan. As ondansetron is now available in
generic formulations, and is relatively inexpensive, it is anticipated that if this study is
positive, ondansetron will be considered for inclusion in the WHO - gastroenteritis care
package. This could ultimately lead to a decrease in the need for intravenous rehydration in
children in countries such as Pakistan. Moreover, these findings will lead to a subsequent
study evaluating its potential benefit in outreach communities where treatments such as
intravenous rehydration are unavailable.
Eligibility
Minimum age: 6 Months.
Maximum age: 59 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age 6 - 59 months (0. 5 - 5 years)
- Symptoms consistent with gastroenteritis (must have a & b)
a. 1 episode of nonbilious, nonbloody vomiting within the 4 hours preceding triage i.
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).
b. Presence of ≥ 1 episode of diarrhea during the illness i. 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 NO dehydration (NO=not enough signs to classify as some or severe
dehydration)
Exclusion Criteria:
- Weight <8 kg
- Vomiting or diarrhea for > 7 days
- Malnutrition: The World Health Organization (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
Locations and Contacts
Stephen Freedman, MD, Phone: (403)955-7740, Email: stephen.freedman@albertahealthservices.ca
Aga Khan University Hospital, Karachi, Pakistan; Recruiting Asghar Ali, Phone: +92 21 3486 4385, Email: asghar.ali@aku.edu Sajid Soofi, MD, Principal Investigator
Aga Khan Hospital for Women and Children (AKHWC), Kharadar, Karachi, Pakistan; Recruiting Asghar Ali, Phone: +92 21 3486 4385, Email: asghar.ali@aku.edu Sajid Soofi, MD, Principal Investigator
Additional Information
Starting date: May 2014
Last updated: September 25, 2014
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