medwireNews: Direct-acting antivirals may reduce the duration of hospitalization for patients with severe influenza versus placebo or standard care; however, the certainty of evidence is low and overall data supporting antiviral use is scarce, report researchers.
Neither oseltamivir, peramivir, nor zanamivir had a significant effect on mortality rate, intensive care unit (ICU) admission, or time to alleviation of symptoms compared with placebo, standard care – or each other – in individuals with severe influenza, show the results of a systematic review and meta-analysis.
“Due to decreasing the rating for risk of bias and imprecision, the certainty of evidence was assessed to be low or very low for all available comparisons and outcomes,” remark Qiukui Hao (McMaster University, Hamilton, Ontario, Canada) and colleagues in The Lancet.
They continue: “Important gaps include better evidence on the effects of antiviral treatment for patients with severe influenza on admission to ICU, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, and emergence of antiviral resistance, and the effects of antivirals on outcomes in key subgroup populations, including patients with severe zoonotic influenza.”
The research team collated data from eight randomized controlled trials involving 1424 individuals and included six in their meta-analysis. All study participants had suspected or laboratory-confirmed influenza and received treatment with either direct-acting influenza antivirals – including oseltamivir, peramivir, zanamivir and baloxavir plus neuraminidase inhibitors – standard care, or placebo.
Hao and co-investigators used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of study evidence, giving each outcome a rating of high, moderate, low, or very low. They judged the certainty of evidence to be low or very low for all study outcomes.
The risk differences for the effect of oseltamivir, peramivir, or zanamivir on mortality from severe seasonal influenza among 813 patients from four of the trials varied from 18 fewer to four more deaths per 1000 patients than with placebo or standard care and were based on very low certainty evidence.
In three trials that included hospitalization duration as an outcome, 226 patients received either oseltamivir, peramivir, standard care, or placebo for severe seasonal influenza. Oseltamivir led to a 1.63-day shorter hospital stay than standard care or placebo, while peramivir shortened the duration by 1.73 days; however, the evidence was of low certainty.
When comparing oseltamivir with peramivir, the researchers observed a mean difference of 0.10 days of hospitalization in favor of oseltamivir, but the evidence was also low certainty.
Similarly, two trials of oseltamivir or peramivir in 235 patients with severe seasonal influenza revealed risk differences of 29 fewer to 43 more admittances to the ICU per 1000 patients compared with those who received placebo or standard care – and these were also graded as being of very low certainty.
Finally, there were “no convincing differences” in the rate of adverse or serious adverse events in the two trials reporting adverse outcomes among 752 patients treated with oseltamivir, peramivir, or zanamivir, report Hao et al.
“Sufficiently powered clinical trials in patients with severe influenza due to seasonal influenza virus infections and novel influenza A virus infections are needed to provide higher certainty evidence of the effects of antiviral treatment on important clinical outcomes,” they therefore conclude.
In an accompanying comment, David Hui (The Chinese University of Hong Kong, China) remarks that while Hao and colleagues found some evidence that antivirals may reduce hospitalization duration, “their findings also highlight the uncertainty regarding the effects of antiviral treatment for patients with severe influenza.”
Hui concludes that “[m]ore randomized controlled trial data are needed” to address the “[m]any knowledge gaps” that need to be filled.
He adds: “Ongoing and large-scale multicentre randomised controlled trials such as the REMAP-CAP and the RECOVERY trial platforms might provide answers to some of these gaps in the near future.”
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