Objetivo
Esta revisión sistemática viva tiene como objetivo entregar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre los efectos de remdesivir en pacientes con COVID-19.

Métodos
Se buscaron ensayos aleatorios que evaluaran el uso de remdesivir versus placebo o ningún tratamiento en pacientes con COVID-19. Se realizó una búsqueda en la plataforma L·OVE COVID-19 (Living OVerview of Evidence), un sistema que mantiene búsquedas regulares en bases de datos, registros de ensayos, servidores preprint y sitios web relevantes en COVID-19. Todas las búsquedas fueron realizadas hasta el 25 de agosto de 2020. No se aplicaron restricciones de fecha ni de idioma. Dos revisores evaluaron de forma independiente los artículos potencialmente elegibles, de acuerdo con criterios de selección predefinidos, y extrajeron los datos mediante un formulario estandarizado. Los resultados fueron combinados mediante un metanálisis utilizando modelos de efectos aleatorios y evaluamos la certeza de la evidencia utilizando el método GRADE. Una versión viva de esta revisión estará abiertamente disponible durante la pandemia de COVID-19.

Resultados
La búsqueda inicial arrojó 574 referencias. Finalmente, identificamos 3 ensayos aleatorios, que evaluaban el uso de remdesivir adicionado al tratamiento estándar versus tratamiento estándar. La evidencia es muy incierta acerca del efecto del remdesivir sobre la mortalidad (RR 0,7; IC del 95%: 0,46 a 1,05; certeza de la evidencia muy baja) y la necesidad de ventilación mecánica invasiva (RR 0,69; IC del 95%: 0,39 a 1,24; certeza de evidencia muy baja). Por otro lado, es probable que el uso de remdesivir produzca un aumento en la incidencia de efectos adversos en pacientes con COVID-19 (RR 1,29; IC del 95%: 0,58 a 2,84; evidencia de certeza moderada).

Conclusiones
La evidencia disponible sobre el papel del remdesivir en el tratamiento de pacientes con COVID-19 es insuficiente en relación a los desenlaces críticos para tomar decisiones, por lo que no es posible realizar un correcto balance entre los beneficios potenciales, los efectos adversos y los costos.

PROSPERO registration number
CRD42020183384

Autores: Francisca Verdugo-Paiva[1,2], María Paz Acuña[3,4], Iván Solá[5,6,7], Gabriel Rada[1,2,8], COVID-19 L·OVE Working Group

Colaboradores:

Filiación:
[1] Epistemonikos Foundation, Santiago, Chile
[2] UC Evidence Center, Cochrane Chile Associated Center, Pontificia Universidad Católica de Chile, Santiago, Chile
[3] Unidad de Infectología, Hospital Dr Sótero del Río, Santiago, Chile
[4] Unidad de Infectología, Hospital Clínico Dra Eloísa Díaz, La Florida, Santiago, Chile
[5] Biomedical Research Institute Sant Pau, Barcelona, Spain
[6] Iberoamerican Cochrane Centre, Barcelona, Spain
[7] CIBER Epidemiología y Salud Pública (CIBERESP)
[8] Internal Medicine Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: fverdugo@epistemonikos.org

Correspondencia a:
[1] Holanda 895
Providencia
Santiago, Chile

Citación: Verdugo-Paiva F, Acuña MP, Solá I, Rada G. Remdesivir for the treatment of COVID-19: a living systematic review. Medwave 2020;20(11):e8080 doi: 10.5867/medwave.2020.11.8080

Fecha de envío: 28/8/2020

Fecha de aceptación: 17/11/2020

Fecha de publicación: 9/12/2020

Origen: No solicitado.

Tipo de revisión: Con revisión externa por tres pares revisores a doble ciego.

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World Health Organization. Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. World Health Organization; 2020 [Accessed 2020 April 12]. [Internet] | Link |

Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Feb;91:264-266. | CrossRef | PubMed |

Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020 May;20(5):533-534. | CrossRef | PubMed |

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. | CrossRef | PubMed |

Tavakoli A, Vahdat K, Keshavarz M. Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century. BPUMS. 2020;22(6):432-450. | CrossRef |

Li LQ, Huang T, Wang YQ, Wang ZP, Liang Y, Huang TB, COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol. 2020 Jun;92(6):577-583. | CrossRef | PubMed |

Global Covid-19 Case Fatality Rates. UK: Centre for Evidence-Based Medicine [Accessed 2020 12 April]. [Internet] | Link |

Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020 Mar-Apr;34:101623. | CrossRef | PubMed |

Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, et al. Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses. J Med Chem. 2017 Mar 9;60(5):1648-1661. | CrossRef | PubMed |

Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017 Jun 28;9(396):eaal3653. | CrossRef | PubMed |

Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020 Sep;585(7824):273-276. | CrossRef | PubMed |

US Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. FDA NEWS RELEASE. 2020

Herper M. Inside the NIH's controversial decision to stop its big remdesivir study. STAT. 2020.

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009 Oct;62(10):1006-12. | CrossRef | PubMed |

Rada G, Verdugo-Paiva F, Ávila C, Morel-Marambio M, Bravo-Jeria R, Pesce F, et al. Evidence synthesis relevant to COVID-19: a protocol for multiple systematic reviews and overviews of systematic reviews. Medwave. 2020 Apr 1;20(3):e7868. | CrossRef | PubMed |

Verdugo F, Acuña MP, Solà I, Rada G. Remdesivir for the treatment of COVID-19: A living systematic review protocol. OSF. 2020. | CrossRef |

Github repository [Accessed 2020 3 April]. [Internet] | Link |

Methods for the special L·OVE of Coronavirus infection. Santiago: Epistemonikos Foundation [Accessed 2020 3 April]. [Internet] | Link |

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019 Aug 28;366:l4898. | CrossRef | Link |

Review Manager (RevMan) [Software]. Version 5.3.5 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008 Apr 26;336(7650):924-6. | CrossRef | PubMed |

Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. J Clin Epidemiol. 2013 Feb;66(2):158-72. | CrossRef | PubMed |

Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, et al. Preparing summary of findings tables and evidence profiles-continuous outcomes. J Clin Epidemiol. 2013 Feb;66(2):173-83. | CrossRef | PubMed |

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. | CrossRef | PubMed |

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-1578. | CrossRef | PubMed |

Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020 Sep 15;324(11):1048-1057. | CrossRef | PubMed |

Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, et al. Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report. medRxiv. 2020.

Borah R, Brown AW, Capers PL, Kaiser KA. Analysis of the time and workers needed to conduct systematic reviews of medical interventions using data from the PROSPERO registry. BMJ Open. 2017 Feb 27;7(2):e012545. | CrossRef | PubMed |

Shojania KG, Sampson M, Ansari MT, Ji J, Doucette S, Moher D. How quickly do systematic reviews go out of date? A survival analysis. Ann Intern Med. 2007 Aug 21;147(4):224-33. | CrossRef | PubMed |

Coronavirus and the risks of 'speed science'. Reuters; 2020 [Accessed 2020 12 April]. [Internet] | Link |

Kelly SE, Moher D, Clifford TJ. Quality of conduct and reporting in rapid reviews: an exploration of compliance with PRISMA and AMSTAR guidelines. Syst Rev. 2016 May 10;5:79. | CrossRef | PubMed |

Elliott JH, Synnot A, Turner T, Simmonds M, Akl EA, McDonald S, et al. Introduction-the why, what, when, and how. J Clin Epidemiol. 2017 Nov;91:23-30. | CrossRef | PubMed |

Akl EA, Haddaway NR, Rada G, Lotfi T. Future of Evidence Ecosystem Series: Evidence synthesis 2.0: when systematic, scoping, rapid, living, and overviews of reviews come together. J Clin Epidemiol. 2020 Jul;123:162-165. | CrossRef | PubMed |