A Randomized, Single-Blind, Group Sequential, Active-Controlled Study to Evaluate the Clinical Efficacy and Safety of α-Lipoic Acid for Critically Ill Patients With Coronavirus Disease 2019 (COVID-19)

  1. Ming Zhong
  2. Aijun Sun
  3. Ting Xiao
  4. Ge Yao
  5. Ling Sang
  6. Xia Zheng
  7. Jinyan Zhang
  8. Xuejuan Jin
  9. Lei Xu
  10. Wenlong Yang
  11. Peng Wang
  12. Kai Hu
  13. Dingyu Zhang
  14. Junbo Ge

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Abstract

To evaluate the clinical efficacy and safety of α-Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19).

Methods

A randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days.

Result

Nine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group ( P = 0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P = 0.09).

Conclusion

In our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19.

Clinical Trial Registration

http://www.chictr.org.cn/showproj.aspx?proj=49534 .

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  1. Version published to 10.3389/fmed.2021.566609
  2. ScreenIT

    SciScore for 10.1101/2020.04.15.20066266: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Ethical approval was obtained from the Institutional Ethics Committee of Zhongshan Hospital(B2020-030).
    Consent: The informed consent was signed by all participants.
    RandomizationStudy design and participants: This study was a randomized, single-blind, group sequential, active-controlled trial.
    Blindingnot detected.
    Power AnalysisStatistical analysis: We estimated that with 10 deaths the study would have 68% power to detect a 50% improvement in survival with ALA versus standard control group (from admission to discharge), at a two-sided alpha level of 0.05.
    Sex as a biological variablenot detected.

    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:
    This trial has several limitations. In particular, the trial did not have sufficient number of cases. Because the epidemic situation in Wuhan was rapidly under control during the trial period, and critically ill COVID patients participating other clinical trials could not be enrolled in this study, only 17 critically ill COVID patients were enrolled in this study. Another limitation is that we use all-cause mortality as our secondary outcome, which could not distinguish death due to primary SARS-COV-2 insult from secondary bacterial infection, which was common in late phrase of critically ill patients with COVID-19. Further clinical studies are needed to verify the promising efficacy of ALA injection in patients with critically ill COVID-19. In conclusion, our results derived from the small number of critically ill COVID patients are promising and hope this report might stimulate the initiation of further clinical studies in larger patient cohort to validate the role of ALA on reducing the short-term mortality rate among critically ill COVID-19 patients.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.04.15.20066266v1 on medRxiv