Primary care patients with influenza-like illness recovered 1 day sooner on average when treated with oseltamivir compared with those receiving usual care only. The results of this study, published in the Lancet, also found that older, sicker patients with comorbidities and longer previous symptom duration recovered 2 to 3 days sooner.
In this open-label, pragmatic, adaptive, randomized controlled trial (ISRCTN Registry identifier: 27908921), 3266 participants in 15 European countries during 3 influenza seasons were recruited. To investigate the benefit of adding oseltamivir to usual care in patients aged >1 year presenting with influenza-like illness in primary care, 1629 patients were allocated to usual care plus oseltamivir, and 1637 to usual care only. The primary outcome of time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent, was determined in 94% and 93% of the groups, respectively. Polymerase chain reaction-confirmed influenza infections occurred in 52% of 3059 participants.
For patients randomly assigned to oseltamivir, time to recovery was shorter overall (hazard ratio [HR], 1.29; 95% Bayesian credible interval [BCrI], 1.20-1.39), as well as in 30 of 36 prespecified subgroups, with estimated hazard ratios ranging from 1.13 to 1.72. Estimated absolute mean benefit from oseltamivir was 1.02 days (95% BCrI, 0.74-1.31) overall. Among the prespecified subgroups, it ranged from 0.70 (95% BCrI, 0.30-1.20) in patients aged <12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration, to 3.20 (95% BCrI, 1.00-5.50) in those aged >65 years with more severe illness, comorbidities, and longer previous illness duration. There was an increased burden of vomiting or nausea observed in the oseltamivir group.
The study was limited by the lack of a placebo control. However, investigators chose to do an open-label trial in the context of everyday practice because the effect sizes identified by a placebo-controlled efficacy study with stricter inclusion criteria might not be reproduced in routine care. Further, researchers were specifically assessing the effect of time to recovery results from the addition of an antiviral to routine care, rather than oseltamivir specifically, and compared this with placebo. This design restricted investigators from knowing the mechanisms or how much of the observed effect is attributable specifically to oseltamivir or other possible effects, and the relative contribution of such possible effects, which might vary among subgroups.
Investigators concluded that the addition of oseltamivir is likely to accelerate recovery by roughly 1 day in in patients with influenza-like illness, and slightly more in those with risk factors. Furthermore, this effect did not appear to be mediated by influenza virus status and is unlikely to be a result of placebo alone. Admittedly, the benefits are modest, and advocating the widespread use of oseltamivir is difficult because of its side- effects and the medicalization of a largely self-limiting illness. However, investigators suggested that, “clinicians and patients might wish to consider adding oseltamivir to routine treatment where a day less of illness is particularly important for patients.” This is especially true in those who are sicker or older, have comorbidities, and have been unwell for longer.
Butler CC, van der Velden AW, Bongard E, et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. Lancet. 2019;395:45-52.