Trial record 11 of 700 for:    Open Studies | "Gastroenteritis"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Calgary
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Thrasher Research Fund
Aga Khan University
Information provided by (Responsible Party):
Sarah Williamson, University of Calgary
ClinicalTrials.gov Identifier:
NCT01870648
First received: May 30, 2013
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

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

Condition Intervention Phase
Dehydration
Gastroenteritis
Vomiting
Diarrhea
Drug: Ondansetron
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ondansetron Administration to Children With Gastroenteritis, Vomiting and SOME Dehydration in Emergency Departments in Pakistan

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Intravenous (IV) Rehydration [ Time Frame: within 72 hours of randomization ] [ Designated as safety issue: No ]
    IV rehydration is defined as the IV administration of ≥20 ml/kg over ≤60 minutes an isotonic fluid for the purpose of rehydration within 72 hours of randomization. This will 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.


Secondary Outcome Measures:
  • The proportion of children who vomit during the 4 hour observation period [ Time Frame: within 4 hour observation period after randomization ] [ Designated as safety issue: No ]
  • The frequency of vomiting during the 4 hour observation period [ Time Frame: within 4 hour observation period after randomization ] [ Designated as safety issue: No ]
  • Hospitalization > 24 hours [ Time Frame: 72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment ] [ Designated as safety issue: No ]
    Total length of stay from Emergency Department (ED) arrival until discharge of > 24 hours, regardless of whether time is spent in the ED or inpatient unit

  • Volume of Oral Rehydration Solution (ORS) consumed (ml/kg) during the 4 hour observation period [ Time Frame: within 4 hour observation period after randomization ] [ Designated as safety issue: No ]
  • Development of "SOME" dehydration during the 72 hours following randomization amongst children who are discharged [ Time Frame: within 72 hours of randomization ] [ Designated as safety issue: No ]
    All children will be presumed to not be dehydrated at the time of discharge regardless of severity of dehydration at the time of ED presentation.

  • Number of diarrheal stools during the 72 hours following randomization [ Time Frame: within 72 hours of randomization ] [ Designated as safety issue: No ]
    Diarrheal stools are defined, in keeping with the WHO definition as "loose or liquid stools"

  • Treatment failure [ Time Frame: 72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment ] [ Designated as safety issue: Yes ]

    This aggregate outcome will include children who experience the following:

    1. IV rehydration as defined in primary outcome
    2. Nasogastric rehydration for > 24 hours - this implies a failure of outpatient Oral Rehydration Therapy (ORT)
    3. Death within 72 hours (from any cause; in or out of hospital)

  • 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) [ Time Frame: 72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Major Side Effects [ Time Frame: 72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment ] [ Designated as safety issue: Yes ]
    Uncommon events such as: Arrythmia and Death. This data is critical to estimate a safety profile of ondansetron in low to middle income countries

  • Semi- and Intensive Care Unit Admission [ Time Frame: 72 hours after randomization; 24 hour follow up as needed; chart review 21 days after enrollment ] [ Designated as safety issue: Yes ]
    This data is critical to estimate a safety profile of ondansetron in low to middle income countries


Estimated Enrollment: 868
Study Start Date: May 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ondansetron

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
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.
Other Name: Zofran
Placebo Comparator: Placebo (sugar pill) Drug: Placebo
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 Name: Sugar Pill

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

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 6 - 59 months (0.5 - 5 years)
  • Symptoms consistent with gastroenteritis (must have a & b)

    1. 1 episode of nonbilious, nonbloody vomiting within the 4 hours preceding triage
    2. Presence of ≥ 1 episode of diarrhea during the illness
  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01870648

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

Locations
Pakistan
Aga Khan Maternal and Child Care Centre Recruiting
Hyderabad, Pakistan
Contact: Asghar Ali    +92 21 3486 4385    asghar.ali@aku.edu   
Principal Investigator: Zulfiqar Bhutta, MD         
Aga Khan University Hospital Recruiting
Karachi, Pakistan
Contact: Asghar Ali    +92 21 3486 4385    asghar.ali@aku.edu   
Principal Investigator: Zulfiqar Bhutta, MD         
Sponsors and Collaborators
Sarah Williamson
Bill and Melinda Gates Foundation
Thrasher Research Fund
Aga Khan University
Investigators
Principal Investigator: Stephen Freedman, MD University of Calgary
Principal Investigator: Zulfiqar Bhutta, MD Aga Khan University - World Health Organization
  More Information

No publications provided

Responsible Party: Sarah Williamson, Research Coordinator, University of Calgary
ClinicalTrials.gov Identifier: NCT01870648     History of Changes
Other Study ID Numbers: RSO1026396
Study First Received: May 30, 2013
Last Updated: May 26, 2014
Health Authority: Pakistan: Drug Regulatory Authority Health Ministry
Pakistan: Research Ethics Committee
Canada: Ethics Review Committee

Keywords provided by University of Calgary:
Low-middle income country
Dehydration
Intravenous Rehydration
Pakistan

Additional relevant MeSH terms:
Gastroenteritis
Dehydration
Diarrhea
Vomiting
Water-Electrolyte Imbalance
Metabolic Diseases
Pathologic Processes
Signs and Symptoms, Digestive
Signs and Symptoms
Gastrointestinal Diseases
Digestive System Diseases
Ondansetron
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
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

ClinicalTrials.gov processed this record on July 24, 2014