Tools for Practice Outils pour la pratique


#261 Antivirals for COVID-19


CLINICAL QUESTION
QUESTION CLINIQUE
 Do treatments such as remdesivir or other anti-virals change patient outcomes in COVID-19 patients?

BOTTOM LINE
RÉSULTAT FINAL
 To date, published RCTs have not demonstrated benefit of treating COVID-19 patients with remdesivir, lopinavir-ritonavir or oseltamivir.  There are signals of potential benefits from one interim analysis of remdesivir and non-statistically different results, but more research is needed. Full publication of studies and ongoing trials will help to answer this question.     


CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

 Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session


EVIDENCE
DONNÉES PROBANTES
 Focusing on randomized, controlled trials (RCTs) as cohort studies of treatments can be misleading.  
  • Currently >300 RCTs evaluating different COVID-19 treatments underway.1 
Remdesivir: 
  • Industry supported, double-blind, placebo-controlled trial of 237 admitted (non-ventilated) patients with confirmed COVID-19, oxygen saturation ≤94% and radiographic pneumonia in Wuhan, China.2  Patients were ~66 years old, and received concomitant antibiotics (~90%), steroids (~70%), or anti-virals (18%). 
    • Outcomes: 
      • 28-day mortality: 14% versus 13% (placebo): no difference.  
      • Duration of mechanical ventilation (days): 7 versus 15.5 (placebo): not statistically different. 
      • Time to clinical improvement: 21 versus 23 days (placebo) not statistically different. 
      • Adverse events leading to medication discontinuation: 12% versus 5% (placebo), number needed to harm=15.  
    • Limitations:  
      • Study ended early (sample size not achieved) due to “outbreak being controlled in Wuhan”. 
      • Baseline imbalances suggest inadequate allocation concealment. 
  • Double-blind, placebo-controlled trial of remdesivir. Information from clinical trial registry3 and interim results available via media release;4 1063 hospitalized patients, oxygen saturation ≤94% and radiographic pneumonia. 
    • Median time to recovery: 11 days versus 15 days (placebo), statistically different. 
    • Mortality (unknown time frame): 8% versus 11.6% (placebo), not statistically different. 
  • Another pharmaceutical company press release reported similar outcomes between 5 and 10 days of remdesivir but did not report whether treatment improved outcomes compared to no remdesivir.5 
  • Other RCTs ongoing.6-8 
Lopinavir-Ritonavir (Kaletra®): 
  • Open-label RCT of 199 admitted COVID-19 positive patients with Sp02 <94% in Wuhan, China.9 Patients randomized to lopinavir-ritonavir for 14 days or usual care. Patients were ~58 years and 60% were men. 
    • Outcomes:  
      • 28-day mortality: 19% lopinavir-ritonavir, 25% usual care: not statistically different. 
      • Time to clinical improvement: no difference: 15 versus 16 days. 
      • Length of ICU stay shorter: 6 versus 11 days (control), not quite statistically different. 
      • Adverse events leading to medication discontinuation: 14%. 
    • Limitations: enrollment suspended when remdesivir became available for clinical trials. 
Oseltamivir:  
  • No RCTs in COVID-19 or other coronaviral infections.10 
Context: 
  • Remdesivir is currently only available in Canada through clinical trials.11 
  • Guidelines do not recommend any COVID-19 specific antiviral treatments.12,13  

Gilbert Bretecher June 6, 2023

antivirals not effective for COVID infections

Latest Tools for Practice
Derniers outils pour la pratique
program image
Bradley LeDrew PharmD candidate

#363 Making a difference in indifference? Medications for apathy in dementia

In patients with dementia, how safe and effective are stimulants, antidepressants, and antipsychotics for treating apathy?
Read Lire 0.25 credits available Crédits disponibles
program image
Allison Paige MD CCFP

#362 Facing the Evidence in Acne, Part I: Oral contraceptives and spironolactone in females

How effective are combined oral contraceptives (COC) and spironolactone for treating acne of at least mild-moderate severity in females?
Read Lire 0.25 credits available Crédits disponibles
program image
Michael R Kolber MD CCFP MSc

#361 Preventing RSV Infections in Infants

How safe and effective are monoclonal antibodies to prevent respiratory syncytial virus (RSV) infections in infants?
Read Lire 0.25 credits available Crédits disponibles
May 8, 2020

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session
Author(s)
Auteur(s)
  • Michael R. Kolber MSc MD CCFP
  • Adrienne J Lindblad BSP ACPR PharmD

1. Sanders JM, Monogue ML, Jodlowski TZ et al. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review. JAMA doi:10.1001/jama.2020.6019

2. Wang Y, Zhang D, Du G et al. Remdesivir in adults with severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial. Lancet Published online April 29, 2020 https://doi.org/10.1016/S0140-6736(20)31022-9

3. National Institute of Allergy and Infectious Disease. Adaptive COVID-19 Treatment Trial. NCT#04280705 from clinicaltrials.gov. Accessed May 1, 2020.

4. National Institutes of Health. NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19 [news release]. Available at: https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 Accessed May 1, 2020.

5. Gilead. Gilead announces results from phase 3 trials of investigational antiviral remdesivir in patients with severe COVID-19 [new release]. Available at: https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-announces-results-from-phase-3-trial-of-investigational-antiviral-remdesivir-in-patients-with-severe-covid-19 Accessed Apr 30, 2020.

6. Cao B et al. A Phase 3 Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Mild and Moderate COVID. NCT# 04252664 from Clinicaltrials.gov. Accessed Apr. 22, 2020

7. Kaiser Permanante. Study to Evaluate the Safety and Antiviral Activity of Remdesivir in Participants With Severe Coronavirus Disease (COVID-19). NCT# 04292899 from Clinicaltrials.gov. Accessed Apr. 22, 2020

8. Kaiser Permanante. Study to Evaluate the Safety and Antiviral Activity of Remdesivir in Participants With Moderate Coronavirus Disease (COVID-19). NCT# 04292730 from Clinicaltrials.gov. Accessed Apr. 22, 2020.

9. Cao B, Wang Y, Wen D et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. NEJM DOI: 10.1056/NEJMoa2001282

10. Rios P, Radhakrishan A, Antony J, et al. Effectiveness and safety of antiviral or antibody treatments for coronavirus: a rapid review. Prepared for the Public Health Agency of Canada. Submitted Feb 25, 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.03.19.20039008v2 Accessed Apr 30, 2020.

11. Coronavirus disease (COVID-19): for health professionals. Available at: https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/health-professionals.html Accessed May 4, 2020.

12. National Institutes of Health. COVID-19 Treatment guidelines. Available at: https://www.covid19treatmentguidelines.nih.gov/introduction/ Accessed May 4, 2020.

13. Ye Z, Rochwerg B, Wang Y et al. Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline. CMAJ 2020. doi: 10.1503/cmaj.200648; early released April 29, 2020. 

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.