Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19—Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT)
M Karolyi, E Pawelka, S Omid, F Koenig, V Kauer, B Rumpf, W Hoepler, A Kuran, H Laferl, T Seitz, M Traugott, V Rathkolb, M Mueller, A Abrahamowicz, C Schoergenhofer, M Hecking, A Assinger, C Wenisch, M Zeitlinger, B Jilma, A Zoufaly
Frontiers in Pharmacology, doi:10.3389/fphar.2022.870493
Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed.
Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials.
ETHICS STATEMENT The studies involving human participants were reviewed and approved and all amendments during the study period were approved by the ethics committee of the Medical University of Vienna and Vienna ethics committee. All methods were carried out in accordance with the ethical principles of the Declaration of Helsinki. All patients included in the trial signed an informed consent form. The patients/participants provided their written informed consent to participate in this study.
AUTHOR CONTRIBUTIONS MK and EP wrote the manuscript. MK, EP, SO, AK, HL, VK, BR, TS, VR, MM, and AgA recruited patients for the study and collected the data. FK and MK were responsible for statistical analysis. AZ, CW, BJ, MH, and MZ conceptualized the idea and designed the study. AZ, BJ, CS, and MH wrote the study protocol and ethics application. AlA, WH, SO, and MT proofread the manuscript and helped interpret the data. AZ, CW, and BJ supervised the study. MZ was responsible for all regulatory and legal aspects of the study.
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2022.870493/ full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors..
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'abstract': '<jats:p><jats:bold>Background:</jats:bold> To date, no oral antiviral drug has proven to be '
'beneficial in hospitalized patients with '
'COVID-19.</jats:p><jats:p><jats:bold>Methods:</jats:bold> In this randomized, controlled, '
'open-label, platform trial, we randomly assigned patients ≥18\xa0years hospitalized with '
'COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or '
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'mortality.</jats:p><jats:p><jats:bold>Results:</jats:bold> 201 patients were included in the '
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'years, and 67% were male. The median time from symptom onset to randomization was 7\xa0days '
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'improvement (HR = 0.67, 95%-CI 0.49–0.90; 9 vs. 11\xa0days, <jats:italic>p</jats:italic> = '
'0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), '
'<jats:italic>p</jats:italic> = 0.036] and a shorter LOS (12 vs. 14\xa0days, '
'<jats:italic>p</jats:italic> = 0.023). A statistically nonsignificant trend toward a lower '
'29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), '
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'observed.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> In patients hospitalized for '
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'trials.</jats:p><jats:p><jats:bold>Systematic Review Registration</jats:bold>: '
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'identifier [NCT04351724, EUDRACT-NR: 2020–001302-30].</jats:p>',
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