Cholera (Disorder)
Conditions
Keywords
Pediatric cholera, Ondansetron, Oral rehydration solution, Vomiting, Dehydration, Intravenous fluids
Brief summary
This Phase IIa randomized controlled trial will evaluate whether a single oral dose of ondansetron can reduce oral rehydration failure in children and adolescents with suspected or confirmed cholera and active vomiting. Approximately 120 participants aged 6 months to 17 years with no or some dehydration will be randomized 1:1 to receive standard cholera care alone or standard care plus oral ondansetron 0.15 mg/kg, up to a maximum dose of 8 mg. The primary outcome is oral rehydration failure within 6 hours, defined as initiation of clinically necessary, unplanned intravenous fluids. Secondary outcomes include vomiting frequency, oral rehydration solution intake, intravenous fluid volume, time to clinical rehydration, length of stay, and safety outcomes.
Detailed description
Cholera can cause rapid fluid loss and severe dehydration, particularly in children. Oral rehydration solution (ORS) is the cornerstone of treatment, but persistent vomiting can interfere with adequate ORS intake and lead to escalation to intravenous fluid therapy. Ondansetron is an antiemetic commonly used in children with acute gastroenteritis, but it has not been formally evaluated for preventing oral rehydration failure in children with cholera. This open-label, randomized, controlled Phase IIa trial will enroll approximately 120 children and adolescents aged 6 months to 17 years at the University Hospital of Brazzaville Cholera Treatment Unit in the Republic of the Congo. Eligible participants will have suspected or confirmed cholera, active vomiting, and no or some dehydration. Participants with severe dehydration or shock will receive immediate guideline-based intravenous rehydration and will not be randomized. Participants will be randomized 1:1 to standard cholera management alone or standard care plus a single oral dose of ondansetron at 0.15 mg/kg, with a maximum dose of 8 mg. The primary endpoint is oral rehydration failure within 6 hours of enrollment, defined as initiation of clinically necessary, unplanned intravenous fluids. Secondary outcomes include vomiting episodes, cumulative ORS intake, intravenous fluid volume, time to clinical rehydration, length of hospital stay, and adverse events. Participants will be observed during hospitalization and will undergo brief follow-up approximately 7 days after enrollment for delayed adverse events.
Interventions
DRUGOndansetron
A single oral dose of ondansetron 0.15 mg/kg, up to a maximum dose of 8 mg, administered at enrollment as an oral tablet or orally disintegrating tablet according to age and ability to swallow.
OTHERStandard Cholera Care
Standard cholera management including oral rehydration solution (ORS), zinc supplementation, antibiotics when indicated, and supportive care according to WHO/GTFCC guidance.
Sponsors
Public Interest Science Center
Thrasher Research Fund
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The trial is open-label for participants and treating clinicians. The primary outcome is adjudicated by a clinician not involved in bedside care who is masked to treatment allocation.
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age 6 months to 17 years * Suspected or confirmed cholera * Active vomiting, defined as at least 1 episode within the preceding 4 hours * No dehydration or some dehydration according to WHO/GTFCC criteria * Parent/guardian able to provide informed consent * Assent from children aged 7 years or older, when applicable
Exclusion criteria
* Severe dehydration or shock requiring immediate intravenous rehydration * Known allergy or contraindication to ondansetron * Congenital long QT syndrome or known arrhythmia * Concurrent use of QT-prolonging medications * Inability to tolerate oral medication * Lack of parent/guardian informed consent or required child assent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral Rehydration Failure | Within 6 hours after enrollment | Proportion of participants requiring clinically necessary, unplanned intravenous fluids because of failure of oral rehydration. The endpoint will be determined using prespecified criteria including persistent vomiting despite supervised ORS, failure to meet minimum weight-based ORS intake targets, and persistent or worsening signs of dehydration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vomiting Episodes | At 4, 6, and 24 hours after enrollment | Number of vomiting episodes recorded for each participant after enrollment. |
| Cumulative Oral Rehydration Solution Intake | During hospitalization, approximately 24-48 hours after enrollment or until discharge | Total volume of oral rehydration solution (ORS) consumed by each participant during the clinical observation period. |
| Total Intravenous Fluid Volume | During hospitalization, approximately 24-48 hours after enrollment or until discharge | Total volume of intravenous fluids administered to each participant during the clinical observation period. |
| Time to Clinical Rehydration | Up to 48 hours after enrollment | Time from enrollment to achievement of clinical rehydration based on standardized clinical assessment. |
| Length of Hospital Stay | Up to 48 hours after enrollment | Duration of hospitalization from enrollment until discharge. |
| Adverse Events | From enrollment through Day 7 | Adverse events will be actively monitored and tabulated by treatment group and severity using CTCAE v5.0. An ECG will be obtained if symptoms suggestive of arrhythmia occur. |
Countries
Republic of the Congo
Contacts
CONTACTArmel Landry Batchi-Bouyou, MD, PhD, MPH
PRINCIPAL_INVESTIGATORArmel Landry Batchi-Bouyou, MD, PhD, MPH
Public Interest Science Center
STUDY_CHAIRJason B, MD, MPH
Massachusetts General Hospital
Outcome results
None listed