Table 3.

Ongoing clinical trials targeting androgen pathways for the treatment of COVID-19 infection

Study name/trial No.	Comparison groups	No. (pts.)	Inclusion criteria	Exclusion criteria	Outcome measures	Expect. DoC
RECOVER/NCT04374279	Standard of care and bicalutamidea versus Standard care only	60	- ≥18 years of age - COVID-19 infection, confirmed by PCR - Require in-pt hospitalization due to COVID-19 with minimal respiratory sxs - Able to provide informed consent	- Unable to take orally; pregnant, or breastfeeding - NIPPV or mech. vent.; > 6L O2 req.; or RR > 30 - Taking bicalutamide, any HT within 1 mo. prior to entry - Hx of cirrhosis or LFTs > 3× the ULN - Hx of MI or CHF within 6 mos., or EF < 40% on echo - Currently on coumadin due to drug-drug interactions	Percentage of patients with clinical improvement at day 7 after randomization	Dec. 2021
NCT04509999	Standard of care and bicalutamideb versus standard of care only	100	- Men ≥ 36 years old with at least one T. ≥ 100.4 F., or new cough, or new dyspnea, and +ve COVID-19 by standard local lab. assay - Men ≥ 18 years but < 36 years old with either new cough, or new dyspnea and documented +ve COVID-19 by standard local lab. assay - Access to working telephone or email - Randomization within 7 days of +ve COVID	- Admission to hospital at time of screening - Inclusion in another RT for COVID therapy - Dx of PCA and/or Rx w/ anti-androgen in the past 3 mos - Current Rx w/ androgen replacement - Requirement for warfarin - Inability to take oral bicalutamide - Known HBV or HCV; liver cirrhosis; or LFTs > 3× ULN	Percent of pts with improved COVID-19 symptoms at day 28	Sept. 2022
NCT04446429	Standard of care and dutasteridec or proxalutamide versus standard of care only	381	- Male; age ≥ 50 years old - Presenting w/ “Gabrin sign,” i.e., androgenetic alopecia (NH grade ≥ III) - Positive COVID-19 in the past 7 days - Not hospitalized for acute respiratory sxs - Willing to provide informed consent	- Pt. enrolled in another study drug for COVID-19 drug - pts. taking an anti-androgen - Hypothyroidism - Not willing to provide informed consent	Percentage of pts hospitalized due to COVID-19 over the one month period	Jan. 2021
HITCH/NCT04397718	Standard of care + degarelix versus standard of care alone	198	- Male veterans admitted to a VA hospital - Age 18 and 85d, admitted to an acute in-pt unit due to COVID-19 - +ve rtPCR assay for SARS-CoV-2 on a NPSS - Severity of illness of level 3, 4 or 5 on ISS - The subject or legal rep. must consent to trial	- Hx of severe hypersensitivity to degarelix - Anti-viral COVID-19 therapies except for remdesivir - Hx of congenital long QT or known hx of prolonged QTc - Pt. is planning to father children within the projected time - Use of systemic glucocorticoids except dexamethasone for COVID; use of hydroxychloroquine, chloroquine, or azithromycin; use of any drug known to prolong QT interval within 30 days of day 1 - MI in the past 6 mos, UA, or NYHA class III/IV heart dse	Primary end point is composite of mortality, ongoing need for hospitalization, or requirement for mech. vent./ECMO at day 15 after randomization	Dec. 2020
COVIDENZA/NCT04475601	Enzalutamidef + standard of care versus standard of care alone	500	- Positive COVID-19 test - Mild to severe symptoms of COVID-19 - Hospitalization - WHO performance status 0–3 - Age above or equal to 50 years - Able to provide informed consent - Estimated expected survival of 1 year	Severe allergy to enzalutamide Pregnant or breast-feeding women Need of immediate mechanical ventilation Current medication includes enzalutamide treatment Hx of CVA, or TIA, or seizure ds., unstable CVD Treatment for HIV, or severe immunosuppressive disease Treatment with tamoxifen, or immunosuppressive agents Treatment with warfarin or NOACs Other serious illness or medical condition	Primary end points are time to worsening of ds. and time to improvement (up to 30 days after inclusion for both worsening and improvement)	May 2022

Abbreviations: ds, disease or disorder; DoC, date of completion; ECMO, extracorporeal membrane oxygenation; hx, history; in-pt, inpatient; ISS, influenza severity scale; NIPPV, non-invasive positive pressure ventilation; NH, Norwood Hamilton; No., number; NOACs, non-vit K antagonist oral anticoagulants; NYHA, New York Heart Association; pt, patient; sxs, symptoms; LFTs, liver function enzymes; mech. vent., mechanical ventilation; NPSS, nasopharyngeal swab sample; O₂, oxygen; +ve, positive; rep, representative; req, requirement; RR, respiratory rate; TIA, transient ischemic attack; UA, unstable angina

^aDose and duration of bicalutamide: 150 mg daily for 7 days. In addition to those listed above, exclusion criteria also include allergy to bicalutamide or other androgen receptor inhibitor

^bDose and duration of bicalutamide: 150 mg daily for up to 28 days. Allergy to bicalutamide or other androgen receptor inhibitors is part of exclusion criteria

^cStandard care in is ivermectin + azithromycin for up to 30 days. In addition, patients in the experimental arm will receive either dutasteride at 0.5 mg daily, or proxalutamide 200 mg daily

^dPatients > 85 years can be enrolled if there is no history of chronic obstructive pulmonary disease (COPD), asthma, cardiovascular disease, hypertension, diabetes mellitus, or active malignancy

^eOther exclusion criteria for HITCH include enrollment in another study drug within 30 days of day 1, planned discharge within 24 h of treatment initiation, known psychiatric or substance abuse disorder that interferes with study, Child-Pugh class C liver disease, use androgen receptor antagonists and agonists within 4 weeks, use of ketoconazole or abiraterone acetate within 2 weeks, use of estrogens or progestins within 2 weeks, and pts unwilling or unable to comply with the study protocol

^fEnzalutamide 160-mg tablets will be given orally once daily for up to 5 days (to be given only during hospitalization and stop if starting mechanical ventilation or at discharge from hospital)