Acute gastroenteritis is responsible for some 600,000 hospitalizations and 5000 deaths a year in the United States. Patients who are unable to tolerate fluid replenishment with oral hydration may need to receive intravenous (IV) fluids in the emergency department or other acute care settings.
Now a double-blind, randomized, placebo-controlled trial suggests that a bimodal, sustained-release tablet of the antiemetic ondansetron could help eliminate the need for antiemetic infusion or rescue agents. A single dose prevented vomiting for 24 hours in 65.6% of patients in the treatment group compared with 54.3% in the placebo group for an 11.4% absolute probability difference (95% confidence interval [CI], 0.3% – 22.4%).
That translated to a statistically significant 21% higher proportion of treatment success in the experimental group, for a relative risk of 1.21 (95% CI, 1.00 – 1.46; P = .04). The researchers defined treatment success as meeting the following criteria from 30 minutes through 24 hours after the first dose: no further vomiting, no rescue medication for nausea or vomiting, and no IV hydration.
The 24-mg investigational tablet (Bekindra, Redhill Biopharma) is designed to deliver therapeutic blood levels of the drug from 30 minutes after ingestion, with activity sustained for as long as 24 hours. “Oral administration could potentially avoid the costs, discomfort, and resources associated with intravenous therapy and lead to fewer ED [emergency department] visits for acute gastroenteritis,” Silverman and coauthors write. They note that the bimodal formulation might eliminate the need for repeated dosing and could reduce recurrent symptoms.
The results are “promising,” gastroenterologist Yamini Natarajan, MD, an assistant professor of medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News. She added, however, “It would be best to see if the benefit can be replicated in a larger diverse population, including older patients, since the average age in the study was 29, and in patients with other medical problems.” Natarajan was not involved in the research.
The study does not prove the superiority of bimodal ondansetron over current oral and sublingual formulations, although the findings suggest that the agent is helpful in treating the nausea and dehydration of acute gastroenteritis, Saleem Chowdhry, MD, a gastroenterologist at the Cleveland Clinic, in Ohio, told Medscape Medical News. “Theoretically, even the currently available formulations of ondansetron can achieve the same effects, but they would have to be taken every 4 to 6 hours.”
He also noted that more than 50% of patients responded to placebo. “This number is quite high and raises the question whether any antiemetic is required in this group of patients.”
The final analysis included 321 of 330 patients treated at 19 US emergency departments and two urgent-care centers. Patients were at least 12 years old (mean age, 29 years), and 60.7% patients were women. The patients had been symptomatic for fewer than 36 hours and had vomited at least twice from presumed gastroenteritis during the previous 4 hours.
They were randomly assigned in a 3:2 ratio (active drug to placebo), with 192 patients in the active group and 129 in the placebo group. Antipyretics, antidiarrheals, proton pump inhibitors, and antacids were allowed. Metoclopramide was the recommended default rescue medication.
Almost all ondansetron patients tolerated the tablet; fewer than 5% regurgitated the drug within 15 minutes of ingestion. “This demonstrates that oral antiemetic treatment is feasible for a substantial portion of symptomatic patients with acute gastroenteritis,” the authors write.
Fourteen patients were hospitalized during the study. Four patients in the ondansetron group and one in the placebo group required hospitalization for treatment failure; the other patients were admitted for nongastroenteritis-related reasons.
Thirty-five patients in the ondansetron group (16.7%) and 28 patients in the placebo group (21.7%) experienced one or more episodes of diarrhea within 24 hours after receiving the first dose. As expected with ondansetron’s safety profile, more patients in the active-treatment arm than in the placebo arm reported constipation (4.7% vs 0.8%) and headache (11.4% vs 5.5%).
Although ondansetron is frequently used in acute care to treat vomiting, no published studies support this off-label use for gastroenteritis, the authors note. Previous studies of antiemetics have yielded conflicting results. A 2015 Cochrane review found no clear evidence of the superiority of any antiemetic over placebo for adults treated in the emergency department.
“To our knowledge, this is the first study to demonstrate that ondansetron is beneficial to treat nausea and vomiting in the adult and adolescent acute care population and the first to specifically evaluate acute gastroenteritis,” the authors write.
In their view, the findings suggest antiemetic treatment could potentially be prescribed outside the traditional clinical setting ― by telephone consultation or in telemedicine. “Further study would be needed to confirm the safety and efficacy of providing antiemesis care in alternative treatment strategies,” they write.
The Infectious Diseases Society of America updated its guidelines on the diagnosis and management of acute gastroenteritis in 2017.
Redhill Biopharma provided full financial and material support to conduct this study and was involved in its design. Silverman reports receiving grants from Northwell Health during the study. The remaining authors, Natarajan, and Chowdry have disclosed no relevant financial relationships.
JAMA Netw Open. Published online November 8, 2019. Full text