Ondansetron Administration to WELL Children With Gastroenteritis Associated Vomiting in EDs in Pakistan - Full Text View

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 vomiting and diarrhea in Pakistan.

Condition	Intervention	Phase
Dehydration Gastroenteritis Vomiting Diarrhea	Drug: Ondansetron Drug: Placebo	Phase 4


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 WELL Children With Gastroenteritis Associated Vomiting in Emergency Departments in Pakistan

Resource links provided by NLM:

MedlinePlus related topics: Dehydration Diarrhea Gastroenteritis Nausea and Vomiting

Drug Information available for: Ondansetron hydrochloride Ondansetron

U.S. FDA Resources

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 4 hours of 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.

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.

SOME Dehydration = 2 or more of the following signs:
- Restlessness, irritability
- Sunken Eyes
- Drinks eagerly, thirsty
- Skin pinch goes back slowly
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:	602
Study Start Date:	May 2014
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	November 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

Show Detailed Description

Eligibility


Ages Eligible for Study:	6 Months to 59 Months (Child)
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 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).
2. 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 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

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: NCT01870635

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 University Hospital	Recruiting
Karachi, Pakistan
Contact: Noshad Ali, MD MPH noshad.ali@aku.edu
Contact: Asghar Ali +92 21 3486 4385 asghar.ali@aku.edu
Principal Investigator: Sajid Soofi, MD
Aga Khan Hospital for Women and Children (AKHWC)	Recruiting
Kharadar, Karachi, Pakistan
Contact: Noshad Ali, MD MPH noshad.ali@aku.edu
Contact: Asghar Ali +92 21 3486 4385 asghar.ali@aku.edu
Principal Investigator: Sajid Soofi, MD

Sponsors and Collaborators

Sarah Williamson-Urquhart

Thrasher Research Fund

Bill and Melinda Gates Foundation

Aga Khan University

Investigators


Principal Investigator:	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

More Information


Responsible Party:	Sarah Williamson-Urquhart, Project Manager, University of Calgary
ClinicalTrials.gov Identifier:	NCT01870635 History of Changes
Other Study ID Numbers:	RSO1026252
Study First Received:	May 30, 2013
Last Updated:	April 20, 2016
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 Diarrhea Vomiting Dehydration Signs and Symptoms, Digestive Signs and Symptoms Gastrointestinal Diseases Digestive System Diseases Water-Electrolyte Imbalance Metabolic Diseases Pathologic Processes 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

ClinicalTrials.gov processed this record on September 26, 2016

Ondansetron Administration to WELL Children With Gastroenteritis Associated Vomiting in EDs in Pakistan (OWEP)