A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data.
Eur Urol
; 81(3): 285-293, 2022 03.
Article
in English
| MEDLINE | ID: covidwho-1568696
ABSTRACT
BACKGROUND:
Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.OBJECTIVE:
To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. DESIGNS, SETTINGS, ANDPARTICIPANTS:
A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. INTERVENTION In COVIDENZA, patients were randomized 21 to 5 d of enzalutamide or standard of care. OUTCOME MEASUREMENTS The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. RESULTS ANDLIMITATIONS:
Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.CONCLUSIONS:
The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. PATIENTSUMMARY:
We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Phenylthiohydantoin
/
Tosyl Compounds
/
Benzamides
/
SARS-CoV-2
/
COVID-19 Drug Treatment
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Androgen Antagonists
/
Anilides
/
Nitriles
Type of study:
Diagnostic study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Long Covid
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
English
Journal:
Eur Urol
Year:
2022
Document Type:
Article
Affiliation country:
J.eururo.2021.12.013
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