A noninferiority randomized open-label pilot study of 3- versus 7-day influenza postexposure prophylaxis with oseltamivir in hospitalized children

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This article discusses a pilot study comparing the effectiveness of 3-day versus 7-day postexposure prophylaxis with oseltamivir in hospitalized children exposed to influenza. The study found that the 3-day prophylaxis was noninferior to the 7-day prophylaxis in terms of efficacy, with no significant differences in adverse events. Additionally, the study showed that the 3-day prophylaxis was associated with lower costs compared to the 7-day prophylaxis. The findings suggest that shorter prophylactic treatment may be just as effective in preventing influenza in children, providing potential cost savings.

Abstract

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (nā€‰=ā€‰28 and nā€‰=ā€‰31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7ā€“100%) versus 93.6% (95% CI 78.6ā€“99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (nā€‰=ā€‰27 and nā€‰=ā€‰29, respectively) showed 100% (95% CI 87.2ā€“100%) and 93.1% (95% CI 77.2ā€“99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Ī”ā€‰=ā€‰6.45 percentage points (p.p.) with 1-sided 95% CI (āˆ’Ā 2.8, āˆ’Ā 1.31, pā€‰=ā€‰0.86; ITT) and Ī”ā€‰=ā€‰6.9 p.p. (1-sided 95% CI āˆ’Ā 2.83, āˆ’Ā 1.27, pā€‰=ā€‰0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, pā€‰<ā€‰0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.

Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

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