Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial – Biochemical)
Flavio A Cadegiani, John Mccoy, Carlos Gustavo Wambier, Andy Goren
Cureus, doi:10.7759/cureus.13047
Background and objective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and subsequent infectivity are mediated by androgens and the androgen receptors through the regulation of transmembrane protease, serine 2 (TMPRSS2). Androgenetic alopecia (AGA) predisposes males to severe coronavirus disease 2019 (COVID-19) disease, while the use of 5-alpha-reductase inhibitors (5ARis) and androgen receptor antagonists reduce COVID-19 disease severity. In this study, we aimed to determine the potential benefit of dutasteride, a commonly used broad and potent 5ARi, as a treatment for COVID-19.
Design, setting, and participants The study was conducted at outpatient clinics. Subjects presented to the clinics with a positive reverse transcription-polymerase chain reaction (RT-PCR) test taken within 24 hours of recruitment. All subjects presented with mild to moderate symptoms.
Interventions Subjects were given either dutasteride 0.5 mg/day or placebo for 30 days or until full COVID-19 remission. All subjects received standard therapy with nitazoxanide 500 mg twice a day for six days and azithromycin 500 mg/day for five days.
Main outcome(s) and measure(s) The main outcome(s) and measure(s) were as follows: time to remission, oxygen saturation (%), positivity rates of RT-PCR-SARS-CoV-2, and biochemical analysis [ultrasensitive C-reactive protein (usCRP), D-dimer, lactate, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), ultrasensitive troponin, and ferritin].
Results Subjects taking dutasteride (n=43) demonstrated reduced fatigue, anosmia, and overall disease duration compared to subjects taking a placebo (n=44) (p<.0001 for all). Compared to the placebo group, on Day seven, subjects taking dutasteride had a higher virologic remission rate (64.3% versus 11.8%; p=.0094), higher clinical recovery rate (84.7% versus 57.5%; p=.03), higher mean [standard deviation: SD] oxygen saturation (97.0% [1.4%] versus 95.7% [2.0%]; p=.02), lower median [Interquartile range: IQR] usCRP (0.34 mg/L [0.23 mg/L-0.66 mg/L] versus 1.47 mg/L [0.70 mg/L-3.37 mg/L]; p<.0001), lower median [IQR] lactate (2.01 mmol/L [1.12 mmol/L-2.43 mmol/L] versus 2.66 mmol/L [2.05 mmol/L-3.55 mmol/L]; p=.0049), lower median [IQR] ESR (5.0 mm/1h [3.0 mm/1h-11.0 mm/1h] versus 14.0 mm/1h [7.25 mm/1h-18.5 mm/1h]; p=.
Additional Information Disclosures
References
Mccoy, Wambier, Vano-Galvan, Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19?, J Cosmet Dermatol,
doi:10.1111/jocd.13455?utm_medium=email&utm_source=transactionDOI record:
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"volume": "19",
"year": "2020"
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"DOI": "10.1111/jdv.17021",
"article-title": "5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia (Epub ahead of print)",
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"year": "2020"
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"volume": "7",
"year": "2020"
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"DOI": "10.1016/j.mehy.2020.110112",
"article-title": "Spironolactone may provide protection from SARS-CoV-2: targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS)",
"author": "Cadegiani FA",
"doi-asserted-by": "publisher",
"journal-title": "Med Hypotheses",
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"volume": "143",
"year": "2020"
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"DOI": "10.1152/ajpendo.00136.2020",
"article-title": "Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension?",
"author": "Cadegiani FA",
"doi-asserted-by": "publisher",
"journal-title": "Am J Physiol Endocrinol Metab",
"key": "ref17",
"unstructured": "Cadegiani FA. Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension?. Am J Physiol Endocrinol Metab. 2020, 318:E587-E588. 10.1152/ajpendo.00136.2020",
"volume": "318",
"year": "2020"
},
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"DOI": "10.1111/jdv.16956",
"article-title": "Androgen receptor genetic variant predicts COVID-19 disease severity: a prospective longitudinal study of hospitalized COVID-19 male patients (Epub ahead of print)",
"author": "McCoy J",
"doi-asserted-by": "publisher",
"journal-title": "J Eur Acad Dermatol Venereol",
"key": "ref18",
"unstructured": "McCoy J, Wambier CG, Herrera S, et al.. Androgen receptor genetic variant predicts COVID-19 disease severity: a prospective longitudinal study of hospitalized COVID-19 male patients (Epub ahead of print). J Eur Acad Dermatol Venereol. 2020, 10.1111/jdv.16956",
"year": "2020"
},
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"DOI": "10.1159/000471752",
"article-title": "Hormonal effects of a 5 alpha-reductase inhibitor (finasteride) on hormonal levels in normal men and in patients with benign prostatic hyperplasia",
"author": "Vermeulen A",
"doi-asserted-by": "publisher",
"journal-title": "Eur Urol",
"key": "ref19",
"unstructured": "Vermeulen A, Giagulli VA, De Schepper P, Buntinx A. Hormonal effects of a 5 alpha-reductase inhibitor (finasteride) on hormonal levels in normal men and in patients with benign prostatic hyperplasia. Eur Urol. 1991, 20:82-86. 10.1159/000471752",
"volume": "20",
"year": "1991"
},
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"DOI": "10.1210/jcem.74.3.1371291",
"article-title": "Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia",
"author": "McConnell JD",
"doi-asserted-by": "publisher",
"journal-title": "J Clin Endocrinol Metab",
"key": "ref20",
"unstructured": "McConnell JD, Wilson JD, George FW, Geller J, Pappas F, Stoner E. Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab. 1992, 74:505-508. 10.1210/jcem.74.3.1371291",
"volume": "74",
"year": "1992"
},
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"DOI": "10.21203/rs.3.rs-88952/v1",
"article-title": "Azithromycin with nitazoxanide, hydroxychloroquine or ivermectin, with or without dutasteride, for early stage COVID-19: an open-label prospective observational study in males with mild-to-moderate COVID-19 (The Pre-AndroCoV Male Trial) [PREPRINT]",
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"year": "2020"
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