UMEM Educational Pearls

The much anticipated REMAP-CAP trial was epublished ahead of print July 12th in Intensive Care Medicine.  It was an RCT investigating four antiviral strategies in critically ill adults with COVID-19: lopinavir-ritonavir, hydroxychloroquine, a combination of the two, and no antiviral therapy (control group).  

Despite the hype around protease inhibitors, hydroxychloroquine, and other unproven therapies in COVID (lookin at you next, Ivermectin...), all three strategies had WORSE outcomes than placebo.  They all decreased organ-support-free days (all reaching statistical significance), which was the primary outcome.  They also all led to longer ICU time, longer time to hospital discharge, and reduced 90 day survival.  Not only does this study show no benefit, it shows fairly convincing signs of harm to these therapies.

 

Bottom Line: Protease inhibitors (e.g. lopinavir-ritonavir) and hydroxychloroquine are unproven therapies for critical COVID-19 infection, and are not recommended.  Providers should focus on interventions with demonstrated benefit, most notably steroids and good supportive/critical care.  

References

Arabi YM, Gordon AC, Derde LPG, Nichol AD, Murthy S, Beidh FA, Annane D, Swaidan LA, Beane A, Beasley R, Berry LR, Bhimani Z, Bonten MJM, Bradbury CA, Brunkhorst FM, Buxton M, Buzgau A, Cheng A, De Jong M, Detry MA, Duffy EJ, Estcourt LJ, Fitzgerald M, Fowler R, Girard TD, Goligher EC, Goossens H, Haniffa R, Higgins AM, Hills TE, Horvat CM, Huang DT, King AJ, Lamontagne F, Lawler PR, Lewis R, Linstrum K, Litton E, Lorenzi E, Malakouti S, McAuley DF, McGlothlin A, Mcguinness S, McVerry BJ, Montgomery SK, Morpeth SC, Mouncey PR, Orr K, Parke R, Parker JC, Patanwala AE, Rowan KM, Santos MS, Saunders CT, Seymour CW, Shankar-Hari M, Tong SYC, Turgeon AF, Turner AM, Van de Veerdonk FL, Zarychanski R, Green C, Berry S, Marshall JC, McArthur C, Angus DC, Webb SA; REMAP-CAP Investigators. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial. Intensive Care Med. 2021 Aug;47(8):867-886. doi: 10.1007/s00134-021-06448-5. Epub 2021 Jul 12. PMID: 34251506; PMCID: PMC8274471.