Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

Autor: Gunst JD; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Staerke NB; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Pahus MH; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Kristensen LH; Department of Medicine, Viborg Regional Hospital, Denmark., Bodilsen J; Department of Infectious Diseases, Aalborg University Hospital, Denmark., Lohse N; Department of Emergency Medicine, Copenhagen University Hospital, Hillerød, Denmark.; Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark., Dalgaard LS; Department of Medicine, Regional Hospital West Jutland, Herning, Denmark., Brønnum D; Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark., Fröbert O; Faculty of Health, Dept. of Cardiology, Örebro University, Sweden., Hønge B; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Internal Medicine, Randers Regional Hospital, Randers, Denmark., Johansen IS; Research Unit for Infectious Diseases, Odense University Hospital, University of Southern Denmark, Denmark., Monrad I; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Erikstrup C; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark., Rosendal R; Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark., Vilstrup E; Department of Medicine, Viborg Regional Hospital, Denmark., Mariager T; Department of Infectious Diseases, Aalborg University Hospital, Denmark., Bove DG; Department of Emergency Medicine, Copenhagen University Hospital, Hillerød, Denmark., Offersen R; Department of Medicine, Regional Hospital West Jutland, Herning, Denmark., Shakar S; Department of Internal Medicine, North Denmark Regional Hospital, Denmark.; Department of Emergency Medicine, North Denmark Regional Hospital, Denmark., Cajander S; Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden., Jørgensen NP; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Internal Medicine, Randers Regional Hospital, Randers, Denmark., Sritharan SS; Department of Medicine, Viborg Regional Hospital, Denmark., Breining P; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark., Jespersen S; Department of Emergency Medicine, Copenhagen University Hospital, Hillerød, Denmark., Mortensen KL; Department of Medicine, Regional Hospital West Jutland, Herning, Denmark., Jensen ML; Department of Medicine, Viborg Regional Hospital, Denmark., Kolte L; Department of Lung and Infectious Diseases, Copenhagen University Hospital, Hillerød, Denmark., Frattari GS; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Larsen CS; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Storgaard M; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Nielsen LP; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Tolstrup M; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Sædder EA; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Østergaard LJ; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Ngo HTT; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Jensen MH; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark., Højen JF; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Kjolby M; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.; DANDRITE, Deptarment of Biomedicine, Aarhus University, Aarhus Denmark.; Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark.; University of Dundee, Scotland, United Kingdom., Søgaard OS; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: EClinicalMedicine [EClinicalMedicine] 2021 May; Vol. 35, pp. 100849. Date of Electronic Publication: 2021 Apr 22.
DOI: 10.1016/j.eclinm.2021.100849
Abstrakt: Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.
Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load.
Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group ( P  = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P  = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log 10 copies/mL ( p  <0·05) and -0·82 log 10 in the placebo group ( P  <0·05).
Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.
Competing Interests: Dr. Mortensen reports a Gilead Travel Grant, outside the submitted work. Dr Østergaard reports personal fees from GlaxoSmithKlinePharma A/S, Gilead Science Denmark A/S, Pfizer A/S, MSD Denmark A/S, and Sanofi Pasteur Europe, outside the submitted work. Dr. Kjolby reports grants from The Lundbeck Foundation, during the conduct of the study; and has or has had stocks in Genmab, Novo Nordisk, Novartis, Amgen, and Regeneron. All other authors have nothing to disclose.
(© 2021 The Authors.)
Databáze: MEDLINE
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