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Currently there are no specific treatments available for acute dengue infection. We considered that rupatadine, a platelet-activating factor receptor inhibitor, might modulate dengue-associated vascular leak. The effects of rupatadine were assessed in vitro, and in a dengue model, which showed that rupatadine significantly reduced endothelial permeability by dengue sera in vitro, and significantly inhibited the increased haematocrit in dengue-infected mice with dose-dependency. We conducted a randomised, placebo-controlled trial in 183 adult patients in Sri Lanka with acute dengue, which showed that rupatadine up to 40 mg daily appeared safe and well-tolerated with similar proportions of adverse events with rupatadine and placebo. Although the primary end-point of a significant reduction in fluid leakage (development of pleural effusions or ascites) was not met, post-hoc analyses revealed small but significant differences in several parameters on individual illness days - higher platelet counts and lower aspartate-aminotransferase levels on day 7 in the rupatadine group compared to the placebo group, and smaller effusions on day 8 in the subgroup of patients with pleural effusions. However, due to the small sample size and range of recruitment time, the potential beneficial effects of rupatadine require further evaluation in large studies focused on recruitment during the early febrile phase.

Original publication

DOI

10.1038/s41598-018-22285-x

Type

Journal article

Journal

Sci Rep

Publication Date

01/03/2018

Volume

8

Keywords

Acute Disease, Adult, Animals, Anti-Allergic Agents, Blood Platelets, Cyproheptadine, Dengue, Dengue Virus, Disease Models, Animal, Double-Blind Method, Endothelium, Female, Histamine Antagonists, Histamine H1 Antagonists, Non-Sedating, Human Umbilical Vein Endothelial Cells, Humans, Male, Mice, Mice, Inbred C57BL, Preliminary Data, Sri Lanka, Treatment Outcome