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,
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'title': '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)',
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'member': '297',
'reference': [ { 'key': 'ref1',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMoa2002032',
'article-title': 'Clinical characteristics of coronavirus disease 2019 in China',
'volume': '382',
'author': 'Guan WJ',
'year': '2020',
'unstructured': 'Guan WJ, Ni ZY, Hu Y, et al.. Clinical characteristics of coronavirus '
'disease 2019 in China. N Engl J Med. 2020, 382:1708-1720. '
'10.1056/NEJMoa2002032',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref2',
'doi-asserted-by': 'publisher',
'DOI': '10.1186/s13293-020-00304-9',
'article-title': 'Impact of sex and gender on COVID-19 outcomes in Europe',
'volume': '11',
'author': 'Gebhard C',
'year': '2020',
'unstructured': 'Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact '
'of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ. 2020, '
'11:29. 10.1186/s13293-020-00304-9',
'journal-title': 'Biol Sex Differ'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.jaad.2020.05.079',
'article-title': 'Androgenetic alopecia present in the majority of patients hospitalized '
'with COVID-19: the "Gabrin sign"',
'volume': '83',
'author': 'Wambier CG',
'year': '2020',
'unstructured': 'Wambier CG, Vaño-Galván S, McCoy J, et al.. Androgenetic alopecia '
'present in the majority of patients hospitalized with COVID-19: the '
'"Gabrin sign". J Am Acad Dermatol. 2020, 83:680-682. '
'10.1016/j.jaad.2020.05.079',
'journal-title': 'J Am Acad Dermatol'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/jocd.13443',
'article-title': 'A preliminary observation: male pattern hair loss among hospitalized '
'COVID-19 patients in Spain - A potential clue to the role of androgens '
'in COVID-19 severity',
'volume': '19',
'author': 'Goren A',
'year': '2020',
'unstructured': 'Goren A, Vaño-Galván S, Wambier CG, et al.. A preliminary observation: '
'male pattern hair loss among hospitalized COVID-19 patients in Spain - A '
'potential clue to the role of androgens in COVID-19 severity. J Cosmet '
'Dermatol. 2020, 19:1545-1547. 10.1111/jocd.13443',
'journal-title': 'J Cosmet Dermatol'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.jaad.2020.07.099',
'article-title': 'Androgenetic alopecia in COVID-19: Compared to age-matched '
'epidemiologic studies and hospital outcomes with or without the Gabrin '
'sign',
'volume': '83',
'author': 'Wambier CG',
'year': '2020',
'unstructured': 'Wambier CG, Vaño-Galván S, McCoy J, Pai S, Dhurat R, Goren A. '
'Androgenetic alopecia in COVID-19: Compared to age-matched epidemiologic '
'studies and hospital outcomes with or without the Gabrin sign. J Am Acad '
'Dermatol. 2020, 83:e453-e454. 10.1016/j.jaad.2020.07.099',
'journal-title': 'J Am Acad Dermatol'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/jdv.16953',
'article-title': 'Anti-androgens may protect against severe COVID-19 outcomes: results '
'from a prospective cohort study of 77 hospitalized men (Epub ahead of '
'print)',
'author': 'Goren A',
'year': '2020',
'unstructured': 'Goren A, Wambier CG, Herrera S, et al.. Anti-androgens may protect '
'against severe COVID-19 outcomes: results from a prospective cohort '
'study of 77 hospitalized men (Epub ahead of print). J Eur Acad Dermatol '
'Venereol. 2020, 10.1111/jdv.16953',
'journal-title': 'J Eur Acad Dermatol Venereol'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'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)',
'author': 'McCoy J',
'year': '2020',
'unstructured': 'McCoy J, Cadegiani FA, Wambier CG, et al.. 5-alpha-reductase inhibitors '
'are associated with reduced frequency of COVID-19 symptoms in males with '
'androgenetic alopecia (Epub ahead of print). J Eur Acad Dermatol '
'Venereol. 2020, 10.1111/jdv.17021',
'journal-title': 'J Eur Acad Dermatol Venereol'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.annonc.2020.04.479',
'article-title': 'Androgen-deprivation therapies for prostate cancer and risk of '
'infection by SARS-CoV-2: a population-based study (N = 4532)',
'volume': '31',
'author': 'Montopoli M',
'year': '2020',
'unstructured': 'Montopoli M, Zumerle S, Vettor R, et al.. Androgen-deprivation therapies '
'for prostate cancer and risk of infection by SARS-CoV-2: a '
'population-based study (N = 4532). Ann Oncol. 2020, 31:1040-1045. '
'10.1016/j.annonc.2020.04.479',
'journal-title': 'Ann Oncol'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.cell.2020.02.052',
'article-title': 'SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a '
'clinically proven protease inhibitor',
'volume': '181',
'author': 'Hoffmann M',
'year': '2020',
'unstructured': 'Hoffmann M, Kleine-Weber H, Schroeder S, et al.. SARS-CoV-2 cell entry '
'depends on ACE2 and TMPRSS2 and is blocked by a clinically proven '
'protease inhibitor. Cell. 2020, 181:271-280. 10.1016/j.cell.2020.02.052',
'journal-title': 'Cell'},
{ 'key': 'ref10',
'doi-asserted-by': 'publisher',
'DOI': '10.1158/2159-8290.CD-13-1010',
'article-title': 'The androgen-regulated protease TMPRSS2 activates a proteolytic cascade '
'involving components of the tumor microenvironment and promotes '
'prostate cancer metastasis',
'volume': '4',
'author': 'Lucas JM',
'year': '2014',
'unstructured': 'Lucas JM, Heinlein C, Kim T, et al.. The androgen-regulated protease '
'TMPRSS2 activates a proteolytic cascade involving components of the '
'tumor microenvironment and promotes prostate cancer metastasis. Cancer '
'Discov. 2014, 4:1310-1325. 10.1158/2159-8290.CD-13-1010',
'journal-title': 'Cancer Discov'},
{ 'key': 'ref11',
'doi-asserted-by': 'publisher',
'DOI': '10.1186/s12916-020-01697-5',
'article-title': 'Polycystic ovary syndrome (PCOS) and COVID-19: an overlooked female '
'patient population at potentially higher risk during the COVID-19 '
'pandemic',
'volume': '18',
'author': 'Kyrou I',
'year': '2020',
'unstructured': 'Kyrou I, Karteris E, Robbins T, Chatha K, Drenos F, Randeva HS. '
'Polycystic ovary syndrome (PCOS) and COVID-19: an overlooked female '
'patient population at potentially higher risk during the COVID-19 '
'pandemic. BMC Med. 2020, 18:220. 10.1186/s12916-020-01697-5',
'journal-title': 'BMC Med'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/jdv.17004',
'article-title': 'Clinical symptoms of hyperandrogenic women diagnosed with COVID-19 '
'(Epub ahead of print)',
'author': 'Cadegiani FA',
'year': '2020',
'unstructured': 'Cadegiani FA, Lim RK, Goren A, et al.. Clinical symptoms of '
'hyperandrogenic women diagnosed with COVID-19 (Epub ahead of print). J '
'Eur Acad Dermatol Venereol. 2020, 10.1111/jdv.17004',
'journal-title': 'J Eur Acad Dermatol Venereol'},
{ 'key': 'ref13',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/jocd.13455',
'article-title': '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?',
'volume': '19',
'author': 'McCoy J',
'year': '2020',
'unstructured': 'McCoy J, Wambier CG, Vano-Galvan S, et al.. 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. '
'2020, 19:1542-1543. 10.1111/jocd.13455',
'journal-title': 'J Cosmet Dermatol'},
{ 'key': 'ref14',
'doi-asserted-by': 'publisher',
'DOI': '10.1186/s12902-020-00626-0',
'article-title': 'Repurposing existing drugs for COVID-19: an endocrinology perspective',
'volume': '20',
'author': 'Cadegiani FA',
'year': '2020',
'unstructured': 'Cadegiani FA. Repurposing existing drugs for COVID-19: an endocrinology '
'perspective. BMC Endocr Disord. 2020, 20:149. 10.1186/s12902-020-00626-0',
'journal-title': 'BMC Endocr Disord'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'DOI': '10.3389/fmed.2020.00453',
'article-title': 'Spironolactone: an anti-androgenic and anti-hypertensive drug that may '
'provide protection against the novel coronavirus (SARS-CoV-2) induced '
'acute respiratory distress syndrome (ARDS) in COVID-19',
'volume': '7',
'author': 'Cadegiani FA',
'year': '2020',
'unstructured': 'Cadegiani FA, Wambier CG, Goren A. Spironolactone: an anti-androgenic '
'and anti-hypertensive drug that may provide protection against the novel '
'coronavirus (SARS-CoV-2) induced acute respiratory distress syndrome '
'(ARDS) in COVID-19. Front Med (Lausanne). 2020, 7:453. '
'10.3389/fmed.2020.00453',
'journal-title': 'Front Med (Lausanne)'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'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)',
'volume': '143',
'author': 'Cadegiani FA',
'year': '2020',
'unstructured': 'Cadegiani FA, Goren A, Wambier CG. Spironolactone may provide protection '
'from SARS-CoV-2: targeting androgens, angiotensin converting enzyme 2 '
'(ACE2), and renin-angiotensin-aldosterone system (RAAS). Med Hypotheses. '
'2020, 143:110112. 10.1016/j.mehy.2020.110112',
'journal-title': 'Med Hypotheses'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'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?',
'volume': '318',
'author': 'Cadegiani FA',
'year': '2020',
'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',
'journal-title': 'Am J Physiol Endocrinol Metab'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'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',
'year': '2020',
'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',
'journal-title': 'J Eur Acad Dermatol Venereol'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'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',
'volume': '20',
'author': 'Vermeulen A',
'year': '1991',
'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',
'journal-title': 'Eur Urol'},
{ 'key': 'ref20',
'doi-asserted-by': 'publisher',
'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',
'volume': '74',
'author': 'McConnell JD',
'year': '1992',
'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',
'journal-title': 'J Clin Endocrinol Metab'},
{ 'key': 'ref21',
'doi-asserted-by': 'publisher',
'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]',
'author': 'Cadegiani FA',
'year': '2020',
'unstructured': 'Cadegiani FA, Goren A, Wambier CG, McCoy J. 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]. Res Sq. 2020, '
'10.21203/rs.3.rs-88952/v1',
'journal-title': 'Res Sq'}],
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'date-time': '2024-02-09T19:29:14Z',
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'URL': 'http://dx.doi.org/10.7759/cureus.13047',
'relation': {},
'ISSN': ['2168-8184'],
'subject': ['Aerospace Engineering'],
'published': {'date-parts': [[2021, 2, 1]]}}
