Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis

Abstract

Introduction

Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients.

Methods

This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April–August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan–Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis.

Results

Overall, median time to discharge was 10 days (95%CI = 9–10) in the favipiravir arm versus 15 days (95%CI = 14–16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56–2.46). Progression to mechanical ventilation was slower with favipiravir (HR_adj = 0.10, 95%CI = 0.04–0.29). There was no significant effect on mortality (HR_adj = 1.56, 95%CI = 0.73–3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HR_adj = 2.80, 95%CI = 0.99–7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings.

Conclusion

Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

Keywords:

• Favipiravir
• effectiveness
• retrospective
• trial
• COVID-19
• mortality
• discharge
• supportive care

Transparency

Declaration of funding

No funding or sponsorship was received for this study or for the publication of this article.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conceptualization: Ahmad Alamer and Ahmad A Alrashed; methodology: Ahmad Alamer and Ivo Abraham; software: Ahmad Alamer; validation: Abdulaziz S. Alulhmim and Ivo Abraham; formal analysis: Ahmad Alamer; data curation: Fatima Alhassar, Malak M. Almutairi, Jude Howaidi, Wedad Almutairi, and Mashael Alfaifi; writing of original draft preparation: Ahmad Alamer and Abdulaziz S. Alulhmim; writing, reviewing, and editing: Ahmad Alamer, Abdulaziz S. Alulhmim, Ivo Abraham, Ahmad A Alrashed, Bandar Alosaimi, Yahya Mohzari, Tarek Sulaiman, Ahmed AlJedai, Alaa H. Alali, and Abdulla Baradwan; visualization: Ahmad Alamer; supervision: Ahmad Alamer and Ivo Abraham; project administration: Ahmad Alamer, Mashael Alfaifi, Ahmad A Alrashed, and Yahya Mohzari. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, declare their responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Acknowledgements

The authors would like to thank the staff at the Research Center at King Fahad Medical City, Riyadh, for their valuable technical support provided for the manuscript. This publication was supported by the Deanship of Scientific Research at Prince Sattam bin Abdulaziz University. The authors would also like to express their gratitude to the staff at the Ministry of Health in Saudi Arabia for their support.

Data availability statement

All data generated or analyzed for this study are included in this published article (and its Supplementary Information files).

Compliance with ethics guidelines

The study was approved by the Institutional Review Boards at KFMC and PMAH (IRB 20-477E, July 2020). Informed consent was waived as this study was considered exempt.