Project Details

Ondansetron administration to children with gastroenteritis associated vomiting in EDs in Pakistan

Stephen Freedman, MDCM, MSc

Summary

BACKGROUND: Vomiting and diarrhea caused by intestinal infection, remains a leading cause of death in children worldwide. Although significant improvements have occurred following the development of a sugar-salt solution which can be administered by mouth to reverse dehydration (oral rehydration) in children who are infected, over a million children continue to die each year. Factors include: (1) many children continue to vomit while receiving oral rehydration; (2) use or oral rehydration has stagnated in low- and middle-income countries (LMIC); (3) and many children lack access to alternatives such as intravenous rehydration. GAP: There is some evidence to suggest that antiemetics may be safe and effective in gastroenteritis however the available data is insufficient as it relates to low- and middle-income countries. We intend to fill this knowledge gap by determining the clinical effectiveness of ondansetron by conducting the first large scale study of ondansetron in a LMIC country. HYPOTHESIS: Children who are administered ondansetron (an antiemetic) will be less likely to receive intravenous rehydration compared to those given placebo. Intravenous rehydration has been selected as the primary outcome as this is a clear outcome which is of paramount importance. Although intravenous fluid administration is available in our study setting, its absence in more rural locations may imply death for children in need. Secondary outcomes will be the frequency of 1) vomiting; 2) hospitalization; 3) dehydration; 4) the volume of oral rehydration solution consumed; and 5) response based on type of infection/illness, duration of illness, and age. METHODS: Two clinical trials will be conducted, one for each level of dehydration severity: either SOME (child displays signs of some dehydration, but not severe) or NONE (child is not dehydrated) determined by the WHO dehydration guidelines. Both trials will be double-blind, placebo controlled randomized trials (ondansetron oral disintegrating tablet compared to a placebo). Total enrollment will be 1470 children; 602 in the NONE group, and 868 children in the SOME group. RESULTS: Pending – The study is still in the recruitment phase. IMPACT: Finding a safe, non-invasive, and effective strategy to reduce vomiting in children could substantially increase the use of oral rehydration and decrease the need for intravenous rehydration. The success of this trial could mean an immediate and readily available (generic and inexpensive) therapeutic intervention that could be expanded to other countries as our proposed intervention could be easily replicated in a variety of LMIC settings, including expansion to administration at a district level as improved ambulatory treatment of gastroenteritis is a priority. Website Link: No study specific website is available however more information can be found at https://clinicaltrials.gov– Identifiers: NCT01870648 & NCT01870635. The study protocol has also been published on Lancet’s website: http://www.thelancet.com/protocol-reviews/14PRT-2519.

Keywords:

Diarrhea, Drug Therapy, Human, Infectious Disease, Randomized Clinical Trial, Treatment