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

• Main Authors: Jesper D. Gunst, Nina B. Staerke, Marie H. Pahus, Lena H. Kristensen, Jacob Bodilsen, Nicolai Lohse, Lars S. Dalgaard, Dorthe Brønnum, Ole Fröbert, Bo Hønge, Isik S. Johansen, Ida Monrad, Christian Erikstrup, Regitze Rosendal, Emil Vilstrup, Theis Mariager, Dorthe G. Bove, Rasmus Offersen, Shakil Shakar, Sara Cajander, Nis P. Jørgensen, Sajitha S. Sritharan, Peter Breining, Søren Jespersen, Klaus L. Mortensen, Mads L. Jensen, Lilian Kolte, Giacomo S. Frattari, Carsten S. Larsen, Merete Storgaard, Lars P. Nielsen, Martin Tolstrup, Eva A. Sædder, Lars J. Østergaard, Hien T.T. Ngo, Morten H. Jensen, Jesper F. Højen, Mads Kjolby, Ole S. Søgaard
• Format: Article
• Language: English
• Published: Elsevier 2021-05-01
• Series: EClinicalMedicine
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589537021001292

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 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. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.