Remdesivir for severe covid-19: a clinical practice guideline

Abstract

Clinical questionWhat is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020.Current practiceRemdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice.RecommendationsThe guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir.How this guideline was createdAn international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems.The evidenceThe linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay.Understanding the recommendationMost patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.

Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review

“…Moreover, remdesivir has been included in the most recent guidelines of National Institute of Health (NIH), USA, for the treatment of COVID-19 patients with mild-moderate disease needing supplemental oxygen, but not requiring high-flow oxygen [75]. On the contrary, an expert panel from Canada recommended remdesivir only for patients with severe disease [76]. However, according to NIH guidelines, remdesivir seems more appropriate during the early phase of COVID-19 disease, preceding the massive cytokine release (Fig.…”

Comparative Effectiveness and Safety of 32 Pharmacological Interventions Recommended by Guidelines for COVID-19: A Systematic Review and Network Meta-Analysis Combining 66 Trials

“…In our study, an increased risk of OAE was detected for CQ and IFN, and diarrhea for LPV_RIT and LPV_RIT_RIB_IFN, although no other signi cant risk of OAE was detected for antiviral agents. Given the potential harms with lack of effectiveness, they are not recommended by several guidelines as treatment for COVID-19, particularly for mild to moderate patients [2][3][4][5] . For severe patients who need supplemental oxygen or intensive care, REM is weakly recommended to shorten the time to clinical improvement 5 .…”

“…Only RCTs written in English or Chinese with available outcome data in which different pharmacological interventions compared in patients with suspected or con rmed SARS-COV-2 or SARS-COV were included. Pharmacological interventions were de ned according to recommended guidelines [2][3][4][5] , including antiviral agents [Ribavirin (RIB), lopinavir/ritonavir (LPV_RIT), Remdesivir (REM), Baloxavir marboxil (BAL), Favipiravir (FAV), Umifenovir (UMI), Azvudine (AZV) and darunavir/cobicistat (DRV_c)], antibiotics [Azithromycin (AZI), Lincocin (LIN), Fluoroquinolone (FLU), Cefperazone-Sulbacta (CEFs), Levo oxacin (LEV) and Quinolone (QUI)], COR, CQ, TCM, CON_PLA, α-Lipoic acid (ALA), Ruxolitinib (RUX), Novaferon (NOV), colchicine (COL), IFN, Octagam (IVIG), SOC and placebo (PLA). The primary outcomes of interest included mortality, cure rate, viral negative conversion and overall adverse events rate (OAE).…”

“…So far, many kinds of drugs in addition to standard of care (SOC) are recommended by different clinical guidelines [2][3][4][5] , including antiviral agents, immune-based therapies [such as corticosteroids (COR), convalescent plasma (CON_PLA) and interferons (IFN)], hydroxychloroquine or chloroquine (CQ), traditional Chinese medicine (TCM) and other adjunctive therapies. However, no speci c drugs were currently proven and nearly all drugs are off-label prescribed 6 .…”

Covid-19: The fatal attraction of herd immunity

“…We are still learning about covid-19. Fear was a factor in the initial response, and patients might have been better served by “ordinary decision making in extraordinary times.”4 In the meantime, the evidence base for treatments, such as convalescent plasma and remdesivir, continues to grow 56. Management approaches in pregnancy, for example, are better informed 78…”