Results from the first randomised controlled trial of antiviral against SARS-CoV-2

Jens Lundgren | Mar 2020 | COVID-19 |

Jens Lundgren
Professor of infectious diseases,
practicing infectious disease specialist,
Department of infectious diseases,
Rigshospitalet,
University of Copenhagen,
Denmark

This COVID-19 perspective was produced by Professor Jens D. Lundgren - one of the world’s leading infectious disease specialists. Jens. D. Lundgren is currently leading a clinical trial of investigational vaccine designed to protect against COVID-19. Jens D. Lundgren is also the founder and member of the steering committee of the HIV in Europe Initiative and in 2015 he was awarded the EACS Award for Excellence in HIV Medicine. Friday 20th March 2020 So, yesterday, the first randomized controlled trial of an antiviral against SARS-CoV-2 infection was published. 1 The drug in question was the well known HIV protease inhibitor lopinavir, the plasma concentration of which is boosted by co-administration of the CYP P450 enzyme inhibitor ritonavir. The trial focused on patients with advanced and serious COVID disease – namely those with pneumonia and reduced ability to saturate blood with oxygen. It was designed as an open-label comparison of the antiviral in combination with standard-of-care compared with standard of care alone. No discernible clinical beneficial effect was observed (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). The study had insufficient power to assess mortality (19% vs 25%, respectively (difference: 5.8% (95% CI: -17 to +6%). No clear effect on viral RNA detection levels were made, although the surrogacy of this for possible clinical benefit is unknown. A total of 14% of those allocated to lopinavir/r stopped prematurely because of adverse drug reactions. Analysis The trial appaers reasonable well conducted, not withstanding the open-label which may have caused some degree of bias in endpoint ascertainment. The sample size was relatively limited (n=199), and hence marginal to adequately rule out a possible clinical benefit overall and clearly in relation to mortality. The results will dampen interest to persue this type of antiviral intervention, at least for use in...