Proxalutamide Improves Lung Injury in Hospitalized COVID-19 Patients – an Analysis of the Radiological Findings of the Proxa-Rescue AndroCoV Trial
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Abstract
Introduction
Antiandrogens are candidates against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) due to host cell entry inhibition by the suppression of TMPRSS2. Proxalutamide is a nonsteroidal anti-androgen (NSAA) with strong antagonism on androgen receptor (AR) and angiotensin-converting enzyme 2 (ACE2). Efficacy of proxalutamide was previously demonstrated for early COVID-19 outpatients, and also reduction of deaths in hospitalized COVID-19 patients. Whether radiological changes would follow the improvement in clinical outcomes with proxalutamide is not established. The present post-hoc analysis aims to evaluate whether proxalutamide improves lung injury observed through chest computerized tomography (CT) scans.
Methods
This is a post-hoc analysis of the radiological findings of The Proxa-Rescue AndroCoV Trial with all enrolled patients from the three participating institutions of the city of Manaus, Brazil, that had at least two chest CT scans during hospitalization. The quantification of lung parenchyma involvement was performed by blinded radiologists with expertise in analysis of COVID-19 images. A first chest CT scan was performed upon randomization and a second CT scan was performed approximately five days later, whenever feasible. Improvement rate was the first endpoint, and relative and absolute changes between the first and second CT scans were the second endpoints.
Results
Of the 395 patients initially evaluated, 77 and 169 patients from the proxalutamide and placebo arms, respectively, were included (n=246). Baseline characteristics and percentage of lung parenchyma affected in the baseline chest CT scan were similar between groups. In the second chest CT scan, the percentage of lungs affected (Median – IQR) was 35.0% (25.0-57.5%) in the proxalutamide group versus 67.5% (50.0-80.0%) in the placebo group (p < 0.001). The absolute and relative change between the second and first chest CT scans (Median – IQR) were -15.0 percent points (p.p.) (−30.0 – 0.0p.p.) and -25.0% (−50.0 – 0.0%) in the proxalutamide group, respectively, and +15.0p.p. (0.0 - +30.0p.p.) and +32.7% (0.0 - +80.0%) in the placebo group, respectively (p < 0.001 for both absolute and relative changes). The improvement rate, i . e ., the percentage of subjects that had improvement from the first to the second CT scan, was 72.3% in the proxalutamide group and 23.1% in the placebo group (p < 0.0001), with an improvement rate ratio (95%CI) of 3.15 (2.32 – 4.28).
Conclusion
Proxalutamide improves lung opacities in hospitalized COVID-19 patients when compared to placebo. ( NCT04728802 )
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SciScore for 10.1101/2021.07.01.21259656: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: The RCT was approved by Brazilian National Ethics Committee of the Ministry of Health, under the approval number 4.513.425 of the process number (CAAE) 41909121.0.0000.5553 (original name of the Ethics Committee: Comitê de Ética em Pesquisa (CEP) do the Comitê Nacional de Ética em Pesquisa (CONEP) do Ministério da Saúde - CEP/CONEP/MS).
IRB: The RCT was approved by Brazilian National Ethics Committee of the Ministry of Health, under the approval number 4.513.425 of the process number (CAAE) 41909121.0.0000.5553 (original name of the Ethics Committee: Comitê de Ética em Pesquisa (CEP) do the Comitê Nacional de Ética em Pesquisa (CONEP) do Ministério da Saúde - …SciScore for 10.1101/2021.07.01.21259656: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: The RCT was approved by Brazilian National Ethics Committee of the Ministry of Health, under the approval number 4.513.425 of the process number (CAAE) 41909121.0.0000.5553 (original name of the Ethics Committee: Comitê de Ética em Pesquisa (CEP) do the Comitê Nacional de Ética em Pesquisa (CONEP) do Ministério da Saúde - CEP/CONEP/MS).
IRB: The RCT was approved by Brazilian National Ethics Committee of the Ministry of Health, under the approval number 4.513.425 of the process number (CAAE) 41909121.0.0000.5553 (original name of the Ethics Committee: Comitê de Ética em Pesquisa (CEP) do the Comitê Nacional de Ética em Pesquisa (CONEP) do Ministério da Saúde - CEP/CONEP/MS).Sex as a biological variable Eligibility criteria: In short, for inclusion, men and women above 18 years old hospitalized due to COVID-19 confirmed with a positive real-time reverse transcription polymerase chain reaction (rtPCR) test for SARS-CoV-2 (Cobas SARS-CoV-2 rtPCR kit test protocol, Roche, USA) were considered. Randomization Trial Design, Setting and Locations: Study design, criteria for eligibility, randomization, procedures, outcomes are described elsewhere. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Exclusion criteria included mechanical ventilation at the time of randomization, known congestive heart failure class III or IV (New York Heart Association) York Heart Associationsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Typical limitations of a post-hoc analysis of a RCT are mostly absent in the present case.13 The number of patients without at least two chest TC scans was significantly higher in the placebo group than in the proxalutamide group, possibly because the number of patients that needed ICU was significantly higher in the placebo group (Table 2). Due to the absence of a mobile CT scan, the performance of a CT scan became unfeasible when patients needed ICU, in particular when they were under mechanical ventilation (Table 2). The present analysis possibly underestimates the efficacy of proxalutamide for hospitalized patients with COVID-19, for two reasons: 1. Patients that had better responses to proxalutamide did not undergo a second CT scan, since they were discharged before five days, when a second chest CT scan would be performed, as per the hospitals protocol. Consequently, the best responders to to proxalutamide were probably selectively removed from analysis: and 2. Patients in the placebo group that had worse progression of the COVID-19 were not able to undergo a second CT scan because most of them needed ICU before five days, which precluded them from a second CT scan. In this way, patients that had better responses to usual care were probably selectively were included in the analysis. In short, this is an analysis that compared the group that responded relatively worse to proxalutamide, and therefore remained in the hospital for a longer period of time, with the group tha...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04728802 Completed Proxalutamide Treatment for Hospitalized COVID-19 Patients Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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