5-Alpha-Reductase Inhibitors Reduce Remission Time of COVID-19: Results From a Randomized Double Blind Placebo Controlled Interventional Trial in 130 SARS-CoV-2 Positive Men

  1. Flávio Adsuara Cadegiani
  2. John McCoy
  3. Carlos Gustavo Wambier
  4. Andy Goren

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Abstract

SARS-CoV-2 entry into type II pneumocytes is depended on the TMPRSS2 proteolytic enzyme. The only known promoter of TMPRSS2 in humans is an androgen response element. As such, androgen sensitivity may be a risk factor for COVID-19. Previously, we have reported a retrospective cohort analysis demonstrating the protective effect of 5-alpha-reductase inhibitors (5ARis) in COVID-19. Men using 5ARis were less likely to be admitted to the ICU than men not taking 5ARis. Additionally, men using 5ARis had drastically reduced frequency of symptoms compared to men not using 5ARis in an outpatient setting. Here we aim to determine if 5ARis will be a beneficial treatment if given after SARS-CoV-2 infection.

Methods

A double-blinded, randomized, prospective, investigational study of dutasteride for the treatment of COVID-19 ( NCT04446429 ). Subjects confirmed positive for SARS-CoV-2 were treated in an outpatient setting. Endpoints for the study were remission times for a predetermined set of symptoms: fever or feeling feverish, cough, shortness of breath, sore throat, body pain or muscle pain/ache, fatigue, headache, nasal congestion, nasal discharge (runny nose), nausea or vomiting, diarrhea, loss of appetite, and loss of taste or smell (Ageusia or Anosmia).

Results

A total of 130 SARS-CoV-2 positive men were included in the study, 64 subjects in the dutasteride arm and 66 subjects in the placebo-controlled group. The differences in the average remission times for fatigue and anosmia or ageusia was statistically different between the groups (5.8 versus 10.1 days for fatigue and 7.3 versus 13.4 days for anosmia or ageusia, in dutasteride and placebo groups, respectively), however, the total remission time was significantly reduced for the men given dutasteride; 9.0 days versus 15.6 days in the placebo group (p < 0.001). Excluding loss of taste and smell the average total remission time was 7.3 days in the dutasteride group versus 11.7 in the placebo arm (p < 0.001).

Conclusion

The total remission time for men using 5ARis was significantly reduced compared to men not taking 5ARis.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.16.20232512: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: The study is registered (clinicaltrial.gov) and conducted with the consent and approval of the Brazilian National Ethics Committee (CAAE: 34110420.2.0000.0008).
    RandomizationStudy Design and Oversight: Potential subjects were recruited to a double-blinded, randomized, prospective, investigational study of anti-androgen treatment of COVID-19 (NCT04446429).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Study Population and Covariates: Males being screened for inclusion in a double-blinded, randomized, prospective, interventional study of anti-androgen treatment of COVID-19 were recruited through social media as well as a mailing list of 10,900 men from the Brazilian health care system registry
    Covariates
    suggested: None
    XLSTAT version 2020.3.1.1008 (Addinsoft, Inc.) was used to perform all statistical analysis.
    XLSTAT
    suggested: (XLSTAT, RRID:SCR_016299)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

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

    IdentifierStatusTitle
    NCT04446429CompletedAnti-Androgen Treatment for COVID-19

    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.

  2. Version published to 10.1101/2020.11.16.20232512v1 on medRxiv