Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: Randomized controlled trial

  1. Mohamed Abdel-Salam Elgohary
  2. Eman Medhat Hasan
  3. Amany Ahmad Ibrahim
  4. Mohamed Farouk Ahmed Abdelsalam
  5. Raafat Zaher Abdel-Rahman
  6. Ashraf Ibrahim Zaki
  7. Mohamed Bakr Elaatar
  8. Mohamed Thabet Elnagar
  9. Mohamed Emam Emam
  10. Mahmoud Moustafa Hamada
  11. Taimour Mohamed Abdel-Hamid
  12. Ahmad Samir Abdel-Hafez
  13. Mohamed G. Seadawy
  14. Ahmad Rashad Fatoh
  15. Mohamed Ali Elsaied
  16. Marwa Abdel-Rahman Sakr
  17. Ahmed Omar Elkady
  18. Mohamed Muawad Shehata
  19. Osama Mohamed Nawar
  20. Mohamed Abu-elnaga Selem
  21. Mohamed Saeed Abd-aal
  22. Hany Hafez Lotfy
  23. Tarek Refaat Elnagdy
  24. Sherine Helmy
  25. Magdy Amin Mubark

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Abstract

Background

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to HCV in the replication process. Sofosbuvir/ledipasvir is an approved drug by the FDA to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection..

Methods

This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings.

Results

Two hundred and fifty patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to ICU (RR=1.17, P=0.776). There was no significant difference between treatment groups regarding Total Leukocyte Count, Neutrophils count, Lymph and Urea.

Conclusion

Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with the new treatment protocols.

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    SciScore for 10.1101/2021.05.19.21257429: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The Institutional Review Board of Armed Forces College of Medicine approved the study (Date: 12-04-2020, S.N.: 14).
    Consent: Patients agreed to sign an informed consent to participate in the current study and that they would not participate in other clinical trials within 30 days from the last administration of the study drugs.
    Sex as a biological variableFemale patients enrolled in the study should have no planned pregnancy for six months, with the administration of proper contraceptive measures within 30 days from the first therapeutic dose of the investigational drugs.
    RandomizationStudy design: This randomized controlled clinical trial is a prospective, comparative, single-blinded (from the patient side), randomized study conducted on 250 patients, divided into two equal groups.
    Blindingnot detected.
    Power AnalysisA minimum of 95 subject in each arm was required to fulfill power of 80%.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    when there are no successful consolidated therapies available during epidemics, there is a tendency to use treatments based on preclinical study findings or observational trials with significant limitations (17). There are currently no known therapies for COVID-19, but many options are being considered, including experimental antivirals (15). Direct antiviral combination therapy such as Ledipasvir/Sofosbuvir demonstrated adequate Efficacy in treating HCV with a good safety profile that included minimal side effects and was well tolerated during treatment (18,19). Antiviral drugs that target particular viral targets are also the most successful way to stop the virus from spreading (20). This single-blinded randomized control study looked at antiviral drugs (Ledipasvir/Sofosbuvir) compared to standard treatment COVID-19. We summarized antiviral mechanism data and findings to subsidize decisions related to COVID-19 pharmacological therapy by providing clinically accessible evidence-based information in a clear interpretation. Also, Chen et al, (2020), recommended the drugs, Epclusa (sofosbuvir / velpatasvir) and Harvoni (sofosbuvir/ledipasvir) for managing COVID-19 infected patients owing to their dual inhibitory actions on two viral enzymes (21). The previous studies (22–25) showed that Sofosbuvir / Daclatasvir regain had a faster time to recover from COVID-19 than Lopinavir/ritonavir, leading to the suggestion of using the Ledipasvir/Sofosbuvir combination as a better treatmen...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04530422CompletedEfficacy of Sofosbuvir Plus Ledipasvir in Egyptian Patients …

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.05.19.21257429v1 on medRxiv