AUTHOR=Karolyi M. , Pawelka E. , Omid S. , Koenig F. , Kauer V. , Rumpf B. , Hoepler W. , Kuran A. , Laferl H. , Seitz T. , Traugott M. , Rathkolb V. , Mueller M. , Abrahamowicz A. , Schoergenhofer C. , Hecking M. , Assinger A. , Wenisch C. , Zeitlinger M. , Jilma B. , Zoufaly A. 

TITLE=Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19—Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT)

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.870493

DOI=10.3389/fphar.2022.870493

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19.</p><p><bold>Methods:</bold> 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 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality.</p><p><bold>Results:</bold> 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, <italic>p</italic> = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), <italic>p</italic> = 0.036] and a shorter LOS (12 vs. 14 days, <italic>p</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%), <italic>p</italic> = 0.089] was observed.</p><p><bold>Conclusion:</bold> 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.</p><p><bold>Systematic Review Registration</bold>: [<ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04351724" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/show/NCT04351724</ext-link>, <ext-link ext-link-type="uri" xlink:href="https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT</ext-link>], identifier [NCT04351724, EUDRACT-NR: 2020–001302-30].</p>