Ondansetron to Prevent Oral Rehydration Failure in Children With Cholera

Oral Ondansetron to Prevent ORS Failure in Children With Cholera: A Phase IIa Trial

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.

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.

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