Five-Day vs 10-Day Postexposure Chemoprophylaxis With Oseltamivir to Prevent Hospital Transmission of Influenza: A Noninferiority Randomized Open-Label Study

Abstract

Background The efficacy and optimal duration of post-exposure influenza prophylaxis with oseltamivir is undetermined in hospital settings where immediate separation from index cases is not feasible. Methods In an open-label non-inferiority randomized clinical trial in a single-center university hospital, the efficacy of 5-day versus 10-day post-exposure prophylaxis with oseltamivir was compared in adult patients exposed to influenza who could not be immediately separated from index influenza cases. Influenza incidence was assessed for 10 days after discontinuing prophylaxis. Results Among 222 exposed patients (median age 75 years; male 119; median Charlson comorbidity index 5), 110 patients were assigned to 5-day group of post-exposure prophylaxis with oseltamivir, and 112 patients to the 10-day group. The median duration of exposure to influenza was 2 days (IQR 1–3 days). In the intention to treat analysis, incidence of influenza was 2/110 (1.8%) in the 5-day group and 0/112 (0%) in the 10-day group (difference, 1.8 percentage points [1-sided 95% CI, –1 to 4.9 p.p.]; P=.77). Conclusions For patients exposed to influenza in a hospital setting, and who were not immediately separated from index cases, post-exposure prophylaxis with oseltamivir resulted in low incidence of nosocomial influenza transmission. Five-day post-exposure prophylaxis was non-inferior to 10-day regimen.

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

“…It needs to be emphasized, that PEP efficacy may depend on the study setting and the question of the difference between a household and a nosocomial contact needs to be recognised. Nevertheless, very high efficacy observed in our study is in line with the corresponding studies set in a hospital environment (97% in the study by Shinjoh, 99% in the study by Ishiguro, and 99% in the study by Lepen) and is generally higher than those observed in household settings 21 , 23 , 26 . It may be attributed to various factors, including patient’s better compliance, the duration of contact (which may be ceased with a transfer to another room or discharge from the hospital, which is not a routine procedure in the majotiry of household contacts), and the contact quality – contact among patients differs substantially from household contact.…”

“…Although the majority of patients were adults, there was a pediatric subgroup (the exact number of children was not specified), which opened the discussion on a possibility of shortening the PEP in children, as well 21 . Similarly, the recent randomized trial from Slovenia aimed to verify the possibility of a shorter PEP regimen by allocating 222 adult patients into 5- or 10-day PEP group; the study confirmed high PEP efficacy with a noninferiority of a shorter PEP course compared to the longer one 26 . There have been no controlled studies which would directly compare differences in hospitalized pediatric population, although a protocol for a prospective, multi-center, single-arm trial has been published and to the best of our knowledge the study is being conducted 27 .…”

Antiviral therapies for influenza

“…Current guideline recommends PEP, with oral oseltamivir or inhaled zanamivir for 7 days, in individuals at very high risk of developing complications from influenza and are unvaccinated, or where vaccination is contraindicated as soon as possible (no later than 48 h) after household exposure to influenza; or to all exposed residents or patients regardless of influenza vaccination history during an influenza outbreak in a long-term care facility or hospital [1]. Studies are now suggesting an even shorter course of PEP in the hospital setting with a 3-day [87] or 5-day oseltamivir regimen [88] could still be effective if the close contacts could be or could not be immediately separated from the index cases respectively. The 3-day regimen is now undergoing a prospective, multicentre, single-arm trial on its efficacy [89].…”