DOI QR코드

DOI QR Code

The effects of remdesivir on mortality and the requirement for mechanical ventilation in patients with COVID-19: a systematic review stratified by disease severity

  • Seungeun Ryoo (Division of Health Technology Assessment, National Evidence-Based Healthcare Collaborating Agency) ;
  • Miyoung Choi (Division of Health Technology Assessment, National Evidence-Based Healthcare Collaborating Agency) ;
  • Su-Yeon Yu (College of Nursing and Health, Kongju National University) ;
  • Young Kyung Yoon (Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine) ;
  • Kyungmin Huh (Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Eun-Jeong Joo (Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine)
  • 투고 : 2023.08.24
  • 심사 : 2023.10.23
  • 발행 : 2024.01.01

초록

Background/Aims: The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. Results: A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. Conclusions: In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilator support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.

키워드

과제정보

This research was supported by National Evidence-based Healthcare Collaborating Agency (NECA-P-21-004, NECA-A-22-008, NECA-A-23-010).

참고문헌

  1. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569-1578.  https://doi.org/10.1016/S0140-6736(20)31022-9
  2. Beigel JH, Tomashek KM, Dodd LE, et al.; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med 2020;383:1813-1826.  https://doi.org/10.1056/NEJMoa2007764
  3. Spinner CD, Gottlieb RL, Criner GJ, et al.; GS-US-540-5774 Investigators. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA 2020;324:1048-1057.  https://doi.org/10.1001/jama.2020.16349
  4. Mahajan L, Singh AP, Gifty. Clinical outcomes of using remdesivir in patients with moderate to severe COVID-19: a prospective randomised study. Indian J Anaesth 2021;65(Suppl 1):S41-S46.  https://doi.org/10.4103/ija.IJA_149_21
  5. Ali K, Azher T, Baqi M, et al.; Canadian Treatments for COVID-19 (CATCO); Association of Medical Microbiology and Infectious Disease Canada (AMMI) Clinical Research Network and the Canadian Critical Care Trials Group. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial. CMAJ 2022;194:E242-E251.  https://doi.org/10.1503/cmaj.211698
  6. Ader F, Bouscambert-Duchamp M, Hites M, et al.; DisCoVeRy Study Group. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Infect Dis 2022;22:209-221.  https://doi.org/10.1016/S1473-3099(21)00485-0
  7. Joo EJ, Ko JH, Kim SE, et al. Clinical and virologic effectiveness of remdesivir treatment for severe coronavirus disease 2019 (COVID-19) in Korea: a nationwide multicenter retrospective cohort study. J Korean Med Sci 2021;36:e83. 
  8. WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet 2022;399:1941-1953.  https://doi.org/10.1016/S0140-6736(22)00519-0
  9. Gottlieb RL, Vaca CE, Paredes R, et al.; GS-US-540-9012 (PINETREE) Investigators. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med 2022;386:305-315.  https://doi.org/10.1056/NEJMoa2116846
  10. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev 2019;10:ED000142. 
  11. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol (Engl Ed) 2021;74:790-799. English, Spanish.  https://doi.org/10.1016/j.recesp.2021.06.016
  12. Kim SB, Ryoo S, Huh K, et al.; Korean Society of Infectious Diseases (KSID). Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency guidelines on the treatment of patients with COVID-19. Infect Chemother 2021;53:166-219.  https://doi.org/10.3947/ic.2021.0303
  13. Guyatt GH, Thorlund K, Oxman AD, et al. GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes. J Clin Epidemiol 2013;66:173-183.  https://doi.org/10.1016/j.jclinepi.2012.08.001
  14. Lee TC, Murthy S, Del Corpo O, et al. Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis. Clin Microbiol Infect 2022;28:1203-1210.  https://doi.org/10.1016/j.cmi.2022.04.018
  15. Beckerman R, Gori A, Jeyakumar S, et al. Remdesivir for the treatment of patients hospitalized with COVID-19 receiving supplemental oxygen: a targeted literature review and meta-analysis. Sci Rep 2022;12:9622. 
  16. Grundeis F, Ansems K, Dahms K, et al. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev 2023;1:CD014962. 
  17. Amstutz A, Speich B, Mentre F, et al. Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir Med 2023;11:453-464.  https://doi.org/10.1016/S2213-2600(22)00528-8
  18. Ferrer M, Travierso C, Cilloniz C, et al. Severe community-acquired pneumonia: characteristics and prognostic factors in ventilated and non-ventilated patients. PLoS One 2018;13:e0191721. 
  19. Klompas M, Branson R, Cawcutt K, et al. Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update. Infect Control Hosp Epidemiol 2022;43:687-713.  https://doi.org/10.1017/ice.2022.88