Bimodal Release Ondansetron for Acute Gastroenteritis Among Adolescents and Adults: A Randomized Clinical Trial

Abstract

Importance: Vomiting resulting from acute gastroenteritis is commonly treated with intravenous antiemetics in acute care settings. If oral treatment were beneficial, patients might not need intravenous administered hydration or medication. Furthermore, a long-acting treatment could provide sustained relief from nausea and vomiting.

Objective: To determine whether an experimental long-acting bimodal release ondansetron tablet decreases gastroenteritis-related vomiting and eliminates the need for intravenous therapy for 24 hours after administration.

Design, setting, and participants: This placebo-controlled, double-blind, randomized clinical trial included patients from 19 emergency departments and 2 urgent care centers in the United States from December 8, 2014, to February 17, 2017. Patients 12 years and older with at least 2 vomiting episodes from presumed gastroenteritis in the previous 4 hours and symptoms with less than 36 hours' duration were randomized using a 3:2 active to placebo ratio. Analyses were performed on an intent-to-treat basis and conducted from June 1, 2017, to November 1, 2017.

Intervention: Bimodal release ondansetron tablet containing 6 mg of immediate release ondansetron and 18 mg of a 24-hour release matrix for a total of 24 mg of ondansetron.

Main outcomes and measures: Treatment success was defined as no further vomiting, no need for rescue medication, and no intravenous hydration for 24 hours after bimodal release ondansetron administration.

Results: Analysis included 321 patients (mean [SD] age, 29.0 [11.1] years; 195 [60.7%] women), with 192 patients in the bimodal release ondansetron group and 129 patients in the placebo group. Treatment successes were observed in 126 patients in the bimodal release ondansetron group (65.6%) compared with 70 patients in the placebo group (54.3%), with an 11.4% (95% CI, 0.3%-22.4%) absolute probability difference. The proportion of treatment success was 21% higher among patients who received bimodal release ondansetron compared with those who received a placebo (relative risk, 1.21; 95% CI, 1.00-1.46; P = .04). In an analysis including only patients with a discharge diagnosis of acute gastroenteritis and no major protocol violations, there were 123 treatment successes (69.5%) in the bimodal release ondansetron group compared with 67 treatment successes (54.9%) in the placebo group (relative risk, 1.27; 95% CI, 1.05-1.53; P = .01). Adverse effects were infrequent and similar to the known safety profile of ondansetron.

Conclusions and relevance: This randomized clinical trial found that a long-acting bimodal release oral ondansetron tablet was an effective antiemetic among adolescents and adults with moderate to severe vomiting from acute gastroenteritis. The drug benefits extended to 24 hours after administration. Bimodal release ondansetron may decrease the need for intravenous access and emergency department care to manage acute gastroenteritis.

Trial registration: ClinicalTrials.gov identifier: NCT02246439.

Figure.. CONSORT Flow Diagram

^aA patient was assigned to receive placebo but erroneously received an unassigned study box that turned out to contain the active drug bimodal release ondansetron. All study boxes and content were of the same appearance and the blinding remained intact. Per intent-to-treat procedure, the data were analyzed by the assigned intervention (placebo group). ^bDisqualifying information obtained after consent but before administration of the study drug included pregnancy, other abnormal blood test results, or abnormal electrocardiogram results.