WITHDRAWN: Proxalutamide (GT0918) Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

Abstract

Background: Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. Study design and methods: A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). 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 <3) were administered proxalutamide 200mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization.Results: 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<0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03 to 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 to follow-up, and 2 patients died from acute respiratory distress syndrome.Conclusion: The hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care. Trial Registration: NCT04446429

Androgens’ Role in Severity and Mortality Rates of COVID-19

“…Based on a clinical study the cure rate of patients with COVID-19 treated with proxalutamide was higher than patients treated with placebo on day 14. Overall mortality decreased by 77.7% in 28 days as well 128 . Substantial improvements seen in immunological, inflammatory and thrombotic markers with proxalutamide can support reduction of hospitalization 129 .…”

Androgen Drives the Expression of SARS-CoV-2 Entry Proteins in Sinonasal Tissue

“…To test the benefit of ADT in early COVID-19, Cadegiani et al treated male COVID-19 outpatients with a short course of androgen blockade (ClinicalTrials.gov Identifier: NCT04446429; EAT-DUTA AndroCoV trial in Brazil). [27][28][29] However, the benefit of ADT in early COVID-19 remains inconclusive, and we are awaiting results from independent trials.…”

SARS-CoV-2 vaccination in androgen sensitive phenotypes – A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients

“…5 alpha-reductase is required to produce active metabolites of testosterone. Hence, 5 alphareductase inhibitors, which modulate ACE2 levels, have been promising in the treatment of SARS-CoV-2 infection, indicating the key status of androgen signaling as well (11,12). In addition, androgen receptors have been found working as transcription promoters for transmembrane protease serine 2 (TMPRSS2), which was utilized as the host entry for SARS-COV2 virus spike proteins, suggesting an essential role of androgen sensitivity plays in SARS-COV2 infection (13).…”