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

• Main Authors: M. Karolyi (Author), E. Pawelka (Author), S. Omid (Author), F. Koenig (Author), V. Kauer (Author), B. Rumpf (Author), W. Hoepler (Author), A. Kuran (Author), H. Laferl (Author), T. Seitz (Author), M. Traugott (Author), V. Rathkolb (Author), M. Mueller (Author), A. Abrahamowicz (Author), C. Schoergenhofer (Author), M. Hecking (Author), A. Assinger (Author), C. Wenisch (Author), M. Zeitlinger (Author), B. Jilma (Author), A. Zoufaly (Author)
• Format: Book
• Published: Frontiers Media S.A., 2022-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2022.870493
• Keywords: tmprss2; SARS-CoV-2; high-dose lopinavir/ritonavir; camostat mesylate; mortality; WHO scale; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 13 (2022)

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 7-category 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.Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].