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

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  • Jesper D Gunst
  • Nina B Staerke
  • Marie H Pahus
  • Lena H Kristensen, Deptarment of Medicine, University of Toronto, Toronto, Canada.
  • ,
  • Jacob Bodilsen, Aalborg Psychiatric University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • ,
  • Nicolai Lohse, Deptarment of Emergency Medicine, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark., Pediatric Department, Hilleroed Hospital, Hilleroed, Denmark, Deptarment of Clinical Medicine
  • ,
  • Lars S Dalgaard
  • Dorthe Brønnum, North Denmark Regional Hospital
  • ,
  • Ole Fröbert, Department of Cardiology, Örebro University Hospital, Örebro
  • ,
  • Bo Hønge
  • Isik S Johansen, From the Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Odense, Denmark; Department of Cardiology, Odense University Hospital, Odense, Denmark.
  • ,
  • Ida Monrad, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Christian Erikstrup
  • Regitze Rosendal, Deptarment of Clinical Immunology, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Emil Vilstrup, Deptarment of Medicine, University of Toronto, Toronto, Canada.
  • ,
  • Theis Mariager, Aalborg Psychiatric University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • ,
  • Dorthe G Bove, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark.
  • ,
  • Rasmus Offersen, Deptarment of Medicine, University of Toronto, Toronto, Canada., Regional Hospital West Jutland
  • ,
  • Shakil Shakar, North Denmark Regional Hospital
  • ,
  • Sara Cajander, Department of Cardiology, Örebro University Hospital, Örebro
  • ,
  • Nis P Jørgensen
  • Sajitha S Sritharan
  • Peter Breining
  • Søren Jespersen, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark.
  • ,
  • Klaus L Mortensen
  • Mads L Jensen, Deptarment of Medicine, University of Toronto, Toronto, Canada.
  • ,
  • Lilian Kolte, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark.
  • ,
  • Giacomo S Frattari, Deptarment of Infectious Diseases, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Carsten S Larsen
  • Merete Storgaard
  • Lars P Nielsen, Deptarment of Clinical Pharmacology, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark., Deptarment of Biomedicine
  • ,
  • Martin Tolstrup
  • Eva A Sædder
  • Lars J Østergaard
  • Hien T T Ngo
  • Morten H Jensen, Deptarment of Health Science and Technology, Aalborg Psychiatric University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark., Steno Diabetes Center, North Jutland, Aalborg University Hospital, Denmark
  • ,
  • Jesper F Højen
  • Mads Kjolby
  • Ole S Søgaard

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. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.

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 log10 copies/mL (p <0·05) and -0·82 log10 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.

Original languageEnglish
JournalEClinicalMedicine
Pages (from-to)100849
ISSN2589-5370
DOIs
Publication statusE-pub ahead of print - 22 Apr 2021

Bibliographical note

© 2021 The Authors.

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