Ondansetron Administration to Children With Gastroenteritis, Vomiting and SOME Dehydration in EDs in Pakistan
Condition: Dehydration; Gastroenteritis; Vomiting; Diarrhea
MeSH terms: Gastroenteritis; Dehydration; Vomiting; Diarrhea
Study type: Interventional
Phase: Phase 4

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
    

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"). The trials will have the following specific aims:

        1. To determine, in children 6 - 59 months of age with AGE with vomiting and diarrhea who
           have "NO" dehydration, if there is a reduction in the proportion of children
           administered IV rehydration in those who receive oral ondansetron in addition to all WHO
           standards of care, compared to those receiving an oral placebo in addition to all WHO
           standards of care.

        2. To determine, in children 6 - 59 months of age with AGE with vomiting and diarrhea who
           have "SOME" dehydration, if there is a reduction in the proportion of children
           administered IV rehydration in those who receive oral ondansetron in addition to all WHO
           standards of care, compared to those receiving an oral placebo in addition to all WHO
           standards of care.

      IV rehydration is a powerful marker of treatment failure and reducing the need for IV
      rehydration therapy in either of these 2 groups of children will be viewed as a significant
      advance by healthcare providers and decision makers. Previous studies of ondansetron have not
      been conducted in low and middle income countries (LMIC), have been of relatively small
      sample sizes, have not employed WHO dehydration scales, and have not focused on young
      children (i.e. <5 years). These will be the first pediatric randomized, double-blind trials,
      in a LMIC, defining the impact of oral ondansetron administration in children with AGE on the
      need for IV rehydration. As such therapy is unavailable to a large number of children in LMIC
      countries, the ability to demonstrate that ondansetron can reduce the use of IV rehydration
      will provide compelling evidence that this drug has the potential to save lives around the
      world. We postulate that oral ondansetron administration to children in LMIC, if beneficial
      in our study population, could serve as a feasible and reliable intervention that is
      available for provision by non-hospital based, outreach, and healthcare providers in remote
      regions of the world.

      This study may 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.
    

Intervention name(s): Ondansetron; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Zofran; Sugar Pill
Intervention MeSH terms: Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Low-middle income country; Dehydration; Intravenous Rehydration; Pakistan