Proxalutamide (GT0918) Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial

McCoy et al., Frontiers in Medicine, doi:10.3389/fmed.2021.668698 (date from preprint), NCT04446429

Dec 2020

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RCT 268 male patients in Brazil, 134 treated with proxalutamide, showing significantly lower hospitalization and mechanical ventilation.

This paper was retracted, however no specific reason is provided, the editors have ignored the authors, and the "external expert" was reportedly funded by Pfizer. For details see1.

The retraction notice states: "The investigation found that the claims made in the conclusions were not adequately supported by the methodology of the study. In particular, as confirmed by an external expert, the process of allocation to treatment and control was not sufficiently random."

The lack of any detail on what conclusion is not supported and why, or details of any issues in randomization, suggests the paper was censored rather than retracted.

Important missing comments or errors? Let us know.

risk of death, 80.0% lower, RR 0.20, p = 0.50, treatment 0 of 134 (0.0%), control 2 of 134 (1.5%), NNT 67, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of mechanical ventilation, 97.1% lower, RR 0.03, p < 0.001, treatment 0 of 134 (0.0%), control 17 of 134 (12.7%), NNT 7.9, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of hospitalization, 91.0% lower, RR 0.09, p < 0.001, treatment 3 of 134 (2.2%), control 35 of 134 (26.1%), NNT 4.2.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. twitter.com, twitter.com/FlavioCadegiani/status/1534716400073326592.twitter.com/FlavioCadegiani/status/1534716400073326592.

McCoy et al., 30 Dec 2020, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 15 authors, study period 15 June, 2020 - 28 July, 2020, censored, see details, trial NCT04446429 (history).

This Paper Proxalutamide All

5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia

J Mccoy

We have previously reported that men with androgenetic alopecia (AGA) are more likely to present with severe COVID-19 symptoms, potentially implicating androgen sensitivity as a risk factor for COVID-19. [1] [2] [3] As such, we hypothesized that 5-alphareductase inhibitors (5ARi) may reduce the severity of COVID-19 disease. To test this hypothesis, we conducted a retrospective cohort analysis on male subjects with laboratory confirmed SARS-CoV-2 infection. The subjects presented at one of five outpatient clinics (Corpometria Institute Brasilia, Brazil) from 15 June to 28 July 2020. At the time of visit, 29 clinical symptoms associated with SARS-CoV-2 infection were documented. For analysis, male subjects with AGA were selected. The frequency of clinical symptoms in males with AGA using 5ARis was compared to those not using 5ARis. Among the men presenting at the clinic, 300 were positive for SARS-CoV-2. Of these, 65 had AGA but were not using 5ARis, and 48 had AGA and were taking a 5ARi for at least six months prior to the study. The only 5ARi used in this cohort was dutasteride (0.5 mg) for the treatment of AGA. Propensity score

Conflicts of interest

References

Clark, Hermann, Cunningham, Wilson, Morrill et al., Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5a-reductase inhibitor, J Clin Endocrinol Metab, doi:10.1111/jdv.17021

Gebhard, Regitz-Zagrosek, Neuhauser, Morgan, Klein, Impact of sex and gender on COVID-19 outcomes in Europe, Biol Sex Differ

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Montopoli, Zumerle, Vettor, Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a populationbased study (n=4532), Ann Oncol, doi:10.1016/j.annonc.2020.04.479

Wambier, Vaño-Galv An, Mccoy, Androgenetic alopecia present in the majority of hospitalized COVID-19 patients -the "Gabrin sign, J Am Acad Dermatol, doi:10.1016/j.jaad.2020.05.079

Wambier, Vaño-Galv An, Mccoy, Pai, Dhurat et al., Androgenetic alopecia in COVID-19: compared to age-matched epidemiologic studies and hospital outcomes with or without the Gabrin sign, J Am Acad Dermatol, doi:10.1016/j.jaad.2020.07.099

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Patients were recruited ' 'from October 21 to December 24, 2020 (clinicaltrials.gov ' 'number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization ' '(COVID-19 8-point ordinal scale &lt;3) were administered proxalutamide 200 mg/day or ' 'placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days ' 'post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving ' 'proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The ' '30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, ' 'P &lt; 0.001. The 30-day hospitalization risk ratio was 0.09; ' '95% confidence interval (CI) 0.03–0.27. Patients in the proxalutamide arm more frequently ' 'reported gastrointestinal adverse events, however, no patient discontinued treatment. In ' 'placebo group, 6 patients were lost during follow-up, and 2 patients died from acute ' 'respiratory distress syndrome. 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