A Trial of Lopinavir-Ritonavir in Covid-19
Alberto Carmona-Bayonas (1) , Paula Jimenez-Fonseca (2) , Eduardo Castañón (3)
TO THE EDITOR
At this dire time in which the scientific community is fighting to mitigate the pandemic caused by SARS-CoV-2, Cao et al. conclude that lopinavir–ritonavir was not associated with clinical improvement over standard care. However, it must be pointed out that this conclusion is a classic example of “absence of evidence is not evidence of absence,”1 unless we were to consider that a difference in survival of 17 percentage points (the lower limit of the confidence interval for the between-group difference of 5.8 percentage points in 28-day mortality) is inconsequential.
We digitalized and reanalyzed the data with a Bayesian Cox proportional-hazards model2,3 and found that there was a 73% posterior probability of a clinical improvement of more than 15% and a 17% probability that the effect was in a region of practical equivalence. Since this trial was underpowered, the results do not sustain the conclusion that lopinavir–ritonavir was ineffective.
This drug combination has a well-known safety profile, and in vitro data indicate that it is active against coronavirus.4 At this critical time, even a modest advantage can entail greater availability of crucial material, such as respirators and beds in the intensive care unit.
CITATION N Engl J Med. 2020 May 21;382(21):e68. doi: 10.1056/NEJMc2008043. Epub 2020 May 5.