Conv. Plasma
Nigella Sativa

All proxalutamide studies
Meta analysis
study COVID-19 treatment researchProxalutamideProxalutamide (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 78% Improvement Relative Risk Mortality (b) 79% Recovery rate 45% Recovery rate (b) 55% primary Hospitalization time 33% Proxalutamide  Cadegiani et al.  LATE TREATMENT  DB RCT Is late treatment with proxalutamide beneficial for COVID-19? Double-blind RCT 778 patients in Brazil (February - April 2021) Lower mortality (p<0.0001) and improved recovery (p<0.0001) Cadegiani et al., Cureus, December 2021 Favors proxalutamide Favors control

Final Results of a Randomized, Placebo-Controlled, Two-Arm, Parallel Clinical Trial of Proxalutamide for Hospitalized COVID-19 Patients: A Multiregional, Joint Analysis of the Proxa-Rescue AndroCoV Trial

Cadegiani et al., Cureus, doi:10.7759/cureus.20691, NCT04728802
Dec 2021  
  Source   PDF   All   Meta
RCT 778 hospitalized patients in Brazil, 423 treated with proxalutamide, showing significantly lower mortality and improved recovery with treatment. NCT04728802 (history) and NCT05126628 (history). Authors note that cases in this trial were predominantly the P.1 Gamma variant, for which proxalutamide may be more effective compared to other variants.
risk of death, 78.0% lower, RR 0.22, p < 0.001, treatment 45 of 423 (10.6%), control 171 of 355 (48.2%), NNT 2.7, adjusted per study, 28 days, Cox proportional hazards.
risk of death, 79.0% lower, RR 0.21, p < 0.001, treatment 34 of 423 (8.0%), control 138 of 355 (38.9%), NNT 3.2, adjusted per study, 14 days, Cox proportional hazards.
recovery rate, RR 0.55, p < 0.001, treatment 423, control 355, adjusted per study, inverted to make RR<1 favor treatment, 28 days, Cox proportional hazards.
recovery rate, RR 0.45, p < 0.001, treatment 423, control 355, adjusted per study, inverted to make RR<1 favor treatment, 14 days, Cox proportional hazards, primary outcome.
hospitalization time, 33.3% lower, relative time 0.67, p < 0.001, treatment 423, control 355.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Cadegiani et al., 25 Dec 2021, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 15 authors, study period 1 February, 2021 - 15 April, 2021, trial NCT04728802 (history).
This PaperProxalutamideAll
Final Results of a Randomized, Placebo-Controlled, Two-Arm, Parallel Clinical Trial of Proxalutamide for Hospitalized COVID-19 Patients: A Multiregional, Joint Analysis of the Proxa-Rescue AndroCoV Trial
Flavio A Cadegiani, Ricardo A Zimerman, Daniel N Fonseca, Michael N Correia, Marcio P Muller, Diego Leonardo Bet, Marcio Rafael Slaviero, Ivan Zardo, Paulo Roberto Benites, Renan N Barros, Raysa W Paulain, Dirce C Onety, Karla Cristina P Israel, Carlos Gustavo Wambier, Andy Goren
Cureus, doi:10.7759/cureus.20691
Background The role of androgens on COVID-19 is well established. Proxalutamide is a second-generation, nonsteroidal antiandrogen (NSAA) with the highest antiandrogen potency among NSAAs and concurrent regulation of angiotensin-converting enzyme 2 (ACE2) expression and inflammatory response. Proxalutamide has been demonstrated to be effective to prevent hospitalizations in early COVID-19 in randomized clinical trials (RCTs). Conversely, in hospitalized COVID-19 patients, preliminary results from two different arms of an RCT (The Proxa-Rescue AndroCoV Trial) also demonstrated a reduction in all-cause mortality. This study aims to report the final, joint results of the two arms (North arm and South arm) of the Proxa-Rescue AndroCoV trial of the two arms (North and South arms) combined, and to evaluate whether COVID-19 response to proxalutamide was consistent across different regions (Northern Brazil and Southern Brazil). Materials and methods Upon randomization, hospitalized COVID-19 patients received either proxalutamide 300mg/day or placebo for 14 days, in addition to usual care, in a proxalutamide:placebo ratio of 1:1 in the North arm and 4:1 in the South arm (ratio was modified due to preliminary report of high drug efficacy). Datasets of the South and North arms were combined, and statistical analysis was performed for the overall study population. Proxalutamide was compared to placebo group for 14-day and 28-day recovery (discharge alive from the hospital) and mortality rates, and overall and post-randomization hospitalization stay. Results of proxalutamide and placebo groups were also compared between the North and South arms. Analysis was also performed stratified by sex and baseline WHO COVID Ordinary Score. Results A total of 778 subjects were included (645 from the North, 317 from the proxalutamide group and 328 from the placebo group; 133 from the South arm, 106 from the proxalutamide group and 27 from the placebo group). Recovery rate was 121% higher in proxalutamide than placebo group at day 14 [81.1% vs 36.6%; Recovery ratio (RecR) 2.21; 95% confidence interval (95% CI), 1.92-2.56; p<0.0001], and 81% higher at day 28 (98.1% vs 47.6%; RecR, 1.81; 95% CI, 1.61-2.03; p<0.0001). All-cause mortality rate was 80% lower in proxalutamide than placebo group at Day 14 [8.0% vs 39.2%; Risk ratio (RR), 0.20; 95% CI, 0.14-0.29; p<0.0001], and 78% lower at Day 28 (10.6% vs 48.2%; RR, 0.22; 95% CI 0.16-0.30). Post-randomization timeto-discharge was shorter in proxalutamide [median, 5 days; interquartile range (IQR), 3-8] than placebo group (median, 9 days; IQR, 6-14) (p<0.0001). Results were statistically similar between North and South arms for all measured outcomes. Males and females presented similar results in all outcomes. Patients that did not require oxygen use (scores 3 and 4) did not present statistically significant improvement in recovery and mortality rates, whereas scores 5 and 6 presented significant improvements in..
Additional Information Disclosures Human subjects: Consent was obtained or waived by all participants in this study. National Ethics Committee (CEP/CONEP/MS) issued approval 4.513.425. The present study was approved by the National Ethics Committee (CEP/CONEP/MS), unrestricted to a specific site, once the research protocol was followed as approved and the study conducted until September 3, 2021, when the approval number to continue the study, in case the study was ongoing, was ceased (the study ended in April 16, 2021) . Approval number 4.513.425; process number (CAAE) 41909121.0.0000.5553. This trial is registered in under two different numbers, one for each arm. (North arm, NCT04728802; South arm, NCT05126628). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: Kintor Pharmaceuticals, Ltd., the manufacturer of proxalutamide, provided the drugs for this trial, and is conducting phase 3 trials for COVID-19. In case efficacy of..
Afar, Vivanco, Hubert, Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia, Cancer Res
Bhowmick, Oft, Dorff, COVID-19 and androgen-targeted therapy for prostate cancer patients, Endocr Relat Cancer, doi:10.1530/ERC-20-0165
Blum, Cimerman, Hunter, Nitazoxanide superiority to placebo to treat moderate COVID-19 -A Pilot prove of concept randomized double-blind clinical trial, EClinicalMedicine, doi:10.1016/j.eclinm.2021.100981
Breithaupt-Faloppa, De, Correia, Prado, Stilhano et al., Estradiol, a potential ally to alleviate SARS-CoV-2 infection, Clinics, doi:10.6061/clinics/2020/e1980
Cadegiani, Fonseca, Correia, Proxalutamide improves lung injury in hospitalized COVID-19 patients -an analysis of the radiological findings of the Proxa-Rescue AndroCoV trial, PREPRINT, doi:10.1101/2021.07.01.21259656
Cadegiani, Fonseca, Mccoy, Efficacy of proxalutamide in hospitalized COVID-19 patients: a randomized, double-blind, placebo-controlled, parallel-design clinical trial, PREPRINT, doi:10.1101/2021.06.22.21259318
Cadegiani, Goren, Wambier, Mccoy, Early COVID-19 therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in outpatient settings significantly improved COVID-19 outcomes compared to known outcomes in untreated patients, New Microbes New Infect, doi:10.1016/j.nmni.2021.100915
Cadegiani, Goren, Wambier, Zimerman, Proxalutamide improves inflammatory, immunologic, and thrombogenic markers in mild-to-moderate COVID-19 males and females: an exploratory analysis of a randomized, double-blinded, placebo-controlled trial early antiandrogen therapy (EAT) with proxalutamide (The EAT-Proxa Biochemical AndroCoV-Trial), PREPRINT), doi:10.1101/2021.07.24.21261047
Cadegiani, Lim, Goren, Clinical symptoms of hyperandrogenic women diagnosed with COVID-19, J Eur Acad Dermatol Venereol, doi:10.1111/jdv.17004
Cadegiani, Lin, Goren, Wambier, Potential risk for developing severe COVID-19 disease among anabolic steroid users, BMJ Case Rep, doi:10.1136/bcr-2021-241572
Cadegiani, Mccoy, Wambier, Goren, 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), Cureus, doi:10.7759/cureus.13047
Cadegiani, Mccoy, Wambier, Proxalutamide significantly accelerates viral clearance and reduces time to clinical remission in patients with mild to moderate COVID-19: results from a randomized, double-blinded, placebo-controlled trial, Cureus, doi:10.7759/cureus.13492
Cadegiani, Repurposing existing drugs for COVID-19: an endocrinology perspective, BMC Endocr Disord, doi:10.1186/s12902-020-00626-0
Cadegiani, Wambier, Goren, 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, doi:10.3389/fmed.2020.00453
Cadegiani, Zimerman, Fonseca, Correia, Mccoy et al., Proxalutamide (GT0918) reduces the rate of hospitalization in mild-to-moderate COVID-19 female patients: a randomized double-blinded placebo-controlled two-arm parallel trial, PREPRINT, doi:10.1101/2021.07.06.21260086
Dambha-Miller, Hinton, Joy, Feher, De Lusignan, Mortality in COVID-19 amongst women on hormone replacement therapy or combined oral contraception: a cohort study, PREPRINT, doi:10.1101/2021.02.16.21251853
Dhindsa, Zhang, Mcphaul, Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19, JAMA Netw Open, doi:10.1001/jamanetworkopen.2021.11398
Durcan, Turan, Bircan, TransCOVID: does gender-affirming hormone therapy play a role in contracting COVID-19?, J Sex Marital Ther, doi:10.1080/0092623X.2021.2000535
Fanning, Zoulim, Hou, Bertoletti, Therapeutic strategies for hepatitis B virus infection: towards a cure, Nat Rev Drug Discov, doi:10.1038/s41573-019-0037-0
Flávio, Zimerman, Goren, Wambier, Proxalutamide Treatment for Hospitalized COVID-19 Patients in Southern Brazil: The South Arm of a Randomized, Double-Blind, Placebo-Controlled, Parallel Clinical Trial -The South Proxa-Rescue AndroCoV Trial
Franceschi, Caldana, Perin, Predominance of the SARS-CoV-2 lineage P.1 and its sublineage P.1.2 in patients from the metropolitan region of Porto Alegre, Southern Brazil in, Pathogens, doi:10.3390/pathogens10080988
Freitas, Lemos, Beckedorff, Cavalcanti, Siqueira et al., The increase in the risk of severity and fatality rate of covid-19 in southern Brazil after the emergence of the Variant of Concern (VOC) SARS-CoV-2 P.1 was greater among young adults without pre-existing risk conditions, doi:10.1101/2021.04.13.21255281
Gebhard, Regitz-Zagrosek, Neuhauser, Morgan, Klein, Impact of sex and gender on COVID-19 outcomes in Europe, Biol Sex Differ, doi:10.1186/s13293-020-00304-9
Ghandehari, Matusov, Pepkowitz, Progesterone in addition to standard of care vs standard of care alone in the treatment of men hospitalized with moderate to severe COVID-19: a randomized, controlled pilot trial, Chest, doi:10.1016/j.chest.2021.02.024
Goren, Wambier, Herrera, Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men, J Eur Acad Dermatol Venereol, doi:10.1111/jdv.16953
Hird, Magee, Bhindi, A systematic review and network meta-analysis of novel androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer, Clin Genitourin Cancer, doi:10.1016/j.clgc.2020.02.005
Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Houghton, Hepatitis C virus: 30 years after its discovery, Cold Spring Harb Perspect Med, doi:10.1101/cshperspect.a037069
Kumar, Zuo, Yalavarthi, SARS-CoV-2 spike protein S1-mediated endothelial injury and proinflammatory state is amplified by dihydrotestosterone and prevented by mineralocorticoid antagonism, Viruses, doi:10.3390/v13112209
Leach, Mohr, Giotis, The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells, Nat Commun, doi:10.1038/s41467-021-24342-y
Lee, Heberer, Gao, A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19 disease incidence and severity, PREPRINT, doi:10.1101/2021.05.10.21255146
Lee, Yousaf, Fang, Kolodney, Male balding is a major risk factor for severe COVID-19, J Am Acad Dermatol, doi:10.1016/j.jaad.2020.07.062
Mccoy, Cadegiani, Wambier, 5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia, J Eur Acad Dermatol Venereol, doi:10.1111/jdv.17021
Mccoy, Goren, Cadegiani, Proxalutamide reduces the rate of hospitalization for COVID-19 male outpatients: a randomized double-blinded placebo-controlled trial, Front Med, doi:10.3389/fmed.2021.668698
Mccoy, Wambier, Herrera, Androgen receptor genetic variant predicts COVID-19 disease severity: a prospective longitudinal study of hospitalized COVID-19 male patients, J Eur Acad Dermatol Venereol, doi:10.1111/jdv.16956
Mcintosh, COVID-19 clinical features
Montopoli, Zumerle, Vettor, Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532), Ann Oncol, doi:10.1016/j.annonc.2020.04.479
Patel, Zhong, Liaw, Tremblay, Tsao et al., Does androgen deprivation therapy protect against severe complications from COVID-19?, Ann Oncol, doi:10.1016/j.annonc.2020.06.023
Qu, Gu, Wang, Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells, Invest New Drugs, doi:10.1007/s10637-020-00901-w
Ranzani, Bastos, Gelli, Marchesi, Baião et al., Characterisation of the first 250,000 hospital admissions for COVID-19 in Brazil: a retrospective analysis of nationwide data, Lancet Respir Med, doi:10.1016/S2213-2600(20)30560-9
Rocco, Silva, Cruz, Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial, Eur Respir J, doi:10.1183/13993003.03725-2020
Salazar Arenas, Del Carpio-Toia, Galdos, Rodriguez-Morales, Alopecia and severity of COVID-19: a cross-sectional study in Peru, Infez Med
Santos, Sayegh, Groehs, Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure, Arq Bras Cardiol, doi:10.5935/abc.20150078
Stasi, Rastrelli, Inglese, Higher testosterone is associated with increased inflammatory markers in women with SARS-CoV-2 pneumonia: preliminary results from an observational study (PREPRINT), J Endocrinol Invest, doi:10.1007/s40618-021-01682-6
Subramanian, Anand, Adderley, Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study, Eur J Endocrinol, doi:10.1530/EJE-20-1163
Taira, Merrick, Galbreath, Butler, Adamovich, Impact of androgen deprivation therapy on overall mortality in prostate brachytherapy patients with low pretreatment testosterone levels, Am J Clin Oncol, doi:10.1097/COC.0000000000000340
Tong, Chen, Wu, Proxalutamide (GT0918), a potent androgen receptor pathway inhibitor, Cancer Res, doi:10.1158/1538-7445.AM2014-614
Velavan, Pallerla, Rüter, Kremsner, Krishna et al., Host genetic factors determining COVID-19 susceptibility and severity, EBioMedicine, doi:10.1016/j.ebiom.2021.103629
Wambier, Mccoy, Goren, Male balding as a major risk factor for severe COVID-19: a possible role for targeting androgens and transmembrane protease serine 2 to protect vulnerable individuals, J Am Acad Dermatol, doi:10.1016/j.jaad.2020.09.015
Wambier, Vaño-Galván, Mccoy, Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: the "Gabrin sign, J Am Acad Dermatol, doi:10.1016/j.jaad.2020.05.079
Wang, Mannan, Xiao, Characterization of SARS-CoV-2 and host entry factors distribution in a COVID-19 autopsy series, Commun Med, doi:10.1038/s43856-021-00025-z
Zhang, Xiang, Huo, Zhou, Jiang et al., Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy, Signal Transduct Target Ther, doi:10.1038/s41392-021-00653-w
Zhao, Lou, Cao, An early assessment of a case fatality risk associated with P.1 SARS-CoV-2 lineage in Brazil: an ecological study, J Travel Med, doi:10.1093/jtm/taab078
Zimerman, Ferrareze, Cadegiani, Comparative genomics and characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern (VOC) from Amazonas, doi:10.1101/2021.10.30.21265694
Zimerman, Fonseca, Correia, Proxalutamide reduction of mortality rate in hospitalized COVID-19 patients depends on treatment duration -an exploratory analysis of the Proxa-Rescue AndroCoV trial, medRxiv, doi:10.1101/2021.06.28.21259661
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop