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.
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| Title: | 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. |
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| Authors: | Cadegiani FA; Internal Medicine, Corpometria Institute, Brasilia, BRA., Zimerman RA; Infectious Disease, Hospital da Brigada Militar de Porto Alegre, Porto Alegre, BRA., Fonseca DN; Internal Medicine, Samel & Oscar Nicolau Hospitals, Manaus, BRA., Correia MN; Internal Medicine, Hospital Regional José Mendes, Itacoatiara, BRA., Muller MP; Surgery, Hospital Arcanjo São Miguel, Gramado, BRA., Bet DL; Internal Medicine, Hospital Unimed Chapecó, Chapecó, BRA., Slaviero MR; Physical Medicine and Rehabilitation, Hospital Arcanjo São Miguel, Gramado, BRA., Zardo I; Cardiology, Hospital Unimed Chapecó, Chapecó, BRA., Benites PR; Pulmonary and Critical Care, Hospital Unimed Chapecó, Chapecó, BRA., Barros RN; Internal Medicine, Hospital Municipal Jofre Cohen, Parintins, BRA., Paulain RW; Internal Medicine, Hospital Municipal Jofre Cohen, Parintins, BRA., Onety DC; Critical Care, Samel & Oscar Nicolau Hospitals, Manaus, BRA., Israel KCP; Nephrology, Samel & Oscar Nicolau Hospitals, Manaus, BRA., Gustavo Wambier C; Dermatology, The Warren Alpert Medical School of Brown University, Providence, USA., Goren A; Dermatology, Applied Biology Inc., Irvine, USA. |
| Source: | Cureus [Cureus] 2021 Dec 25; Vol. 13 (12), pp. e20691. Date of Electronic Publication: 2021 Dec 25 (Print Publication: 2021). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cureus, Inc Country of Publication: United States NLM ID: 101596737 Publication Model: eCollection Cited Medium: Print ISSN: 2168-8184 (Print) Linking ISSN: 21688184 NLM ISO Abbreviation: Cureus Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Palo Alto, CA : Cureus, Inc. |
| Abstract: | Background The role of androgens on COVID-19 is well established. Proxalutamide is a second-generation, non-steroidal 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 time-to-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 all outcomes (p<0.0001 for all). Conclusion Proxalutamide increased recovery rate, reduced mortality rate and shortened hospital stay in hospitalized COVID-19 patients. Results were similar between the two different arms, providing further consistency for the efficacy of proxalutamide when used in late-stage COVID-19. (Copyright © 2021, Cadegiani et al.) |
| Competing Interests: | 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 proxalutamide for COVID-19 is confirmed, Kintor Pharmaceuticals, Ltd. plans to market proxalutamide for COVID-19. AG and FAC were consultants for Applied Biology, Inc. FAC has served in the past as a clinical director for Applied Biology, Inc. CGW has served as an advisor to Applied Biology, Inc. The other authors have no conflict of interest to declare. |
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| Contributed Indexing: | Keywords: androgen receptor; antiandrogens; clinical trial; covid-19; pandemic; proxalutamide; sars-cov-2; sepsis; tmprss2; transmembrane protease serine 2 |
| Entry Date(s): | Date Created: 20220103 Latest Revision: 20240405 |
| Update Code: | 20250114 |
| PubMed Central ID: | PMC8712234 |
| DOI: | 10.7759/cureus.20691 |
| PMID: | 34976549 |
| Database: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Background The role of androgens on COVID-19 is well established. Proxalutamide is a second-generation, non-steroidal 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 time-to-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 all outcomes (p<0.0001 for all). Conclusion Proxalutamide increased recovery rate, reduced mortality rate and shortened hospital stay in hospitalized COVID-19 patients. Results were similar between the two different arms, providing further consistency for the efficacy of proxalutamide when used in late-stage COVID-19.<br /> (Copyright © 2021, Cadegiani et al.) |
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| ISSN: | 2168-8184 |
| DOI: | 10.7759/cureus.20691 |