NCT04729491

EAT-DUTA AndroCoV Trial

Completed Phase 2, PHASE3 Last updated 28 January 2021

What this trial tests

Phase 2, PHASE3 trial testing Dutasteride 0.5 mg in Covid19 in 138 participants. Completed in 7 October 2020.

Timeline

30 June 2020

Primary endpoint
15 September 2020

7 October 2020

Quick facts

Lead sponsor	Corpometria Institute
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	138
Start date	30 June 2020
Primary completion	15 September 2020
Estimated completion	7 October 2020
Sites	1 location across Brazil

Drugs / interventions tested

• Dutasteride 0.5 mg — full drug profile →
• Azithromycin (azithromycin) — full drug profile →
• Nitazoxanide (NITAZOXANIDE) — full drug profile →
• Placebo

Conditions studied

• Covid19 — all drugs for Covid19 →

Sponsor

Corpometria Institute

Who can join

18 and older, male only, with Covid19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a significant difference in the rate of severe cases between adult females and adult males (42% vs 58%). Among children under the age of 14, the rate of severe cases was reported to be extremely low. To explain this difference, several theories have been proposed including cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in severe cases as well as reduced risk in pre-pubescent children. Our past research on male androgenetic alopecia (AGA) has led us to investigate an association between androgens and COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant variation between men and women as well as between adults and pre-pubescent children.

SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2). TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of influenza A and influenza B into primary human airway cells and type II pneumocytes.

The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen receptor.10 Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is affected by male sex hormones with higher activity found in males.

Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common form of hair loss among men. The development of androgenetic alopecia is androgen mediated and is dependent on genetic variants found in the androgen receptor gene located on the X chromosome. We hypothesized that men with AGA would be more prone to severe COVID-19 disease. We conducted a preliminary observational study of hospitalized COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range 23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of AGA was performed clinically by a dermatologist. The precise prevalence of AGA among otherwise healthy Spanish Caucasian males is unknown; however, based on published literature, the expected prevalence of a similar age-matched Caucasian population is approximately 31-53%.

Further, according to the European Center for Disease Control and Prevention (https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-rapid-risk-assessment-coronavirus-disease-2019-eighth-update-8-april-2020.pdf): "Of the confirmed cases in China, 3.8% (1 716/44 672) were healthcare workers. Of those, 14.8% were severely or critically ill and 5% of the severe cases died. Latest figures reported from Italy show that 9% of COVID-19 cases are healthcare workers, with Lombardy region reporting up to 20% of cases in healthcare workers. In Spain, the latest COVID-19 situation overview from the Ministry of Health reports that 26% of COVID-19 cases are in healthcare workers. In a Dutch study, healthcare workers were tested voluntarily for COVID-19 and 6% tested positive. In a report on 30 cases in healthcare workers in China, all cases had a history of direct contact (distance within 1 metre) with COVID-19 patients, with an average number of 12 contacts, and the average cumulative contact time being two hours (1.5, 2.7). In the Dutch study, only 3% of the healthcare workers reported being exposed to hospital patients with COVID-19 prior onset of symptoms and 63% had worked while asymptomatic.

Based on the scientific rationale combined with this preliminary observation, we propose to test an anti-androgen as a treatment for patients recently diagnosed with COVID-19. This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection, including reduction of virological duration and disease severity.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
   Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
2. Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?
   Lott N, Gebhard CE, Bengs S, Haider A, et al · · 2023 · cited 30× · PMID 36494595 · DOI 10.1038/s41574-022-00780-6
3. Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity.
   Spini A, Giudice V, Brancaleone V, Morgese MG, et al · · 2021 · cited 21× · PMID 34454035 · DOI 10.1016/j.phrs.2021.105848
4. COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.
   Kumar S, Basu M, Ghosh P, Pal U, et al · · 2023 · cited 7× · PMID 37334160 · DOI 10.1016/j.gendis.2022.12.019
5. TMPRSS2 as a Key Player in Viral Pathogenesis: Influenza and Coronaviruses.
   Barros de Lima G, Nencioni E, Thimoteo F, Perea C, et al · · 2025 · cited 6× · PMID 39858469 · DOI 10.3390/biom15010075
6. Serendipity for the intervention of COVID-19 and prostatic adenocarcinoma (PaC).
   Naseer F, Ahmad T, Gul R, Anjum S. · · 2022 · cited 1× · PMID 35273376 · DOI 10.1038/s41391-022-00502-z