TY - JOUR

T1 - Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

AU - Gunst, Jesper D.

AU - Staerke, Nina B.

AU - Pahus, Marie H.

AU - Kristensen, Lena H.

AU - Bodilsen, Jacob

AU - Lohse, Nicolai

AU - Dalgaard, Lars Skov

AU - Brønnum, Dorthe

AU - Fröbert, Ole

AU - Hønge, Bo

AU - Johansen, Isik S.

AU - Monrad, Ida

AU - Erikstrup, Christian

AU - Rosendal, Regitze

AU - Vilstrup, Emil

AU - Mariager, Theis

AU - Bove, Dorthe G.

AU - Offersen, Rasmus

AU - Shakar, Shakil

AU - Cajander, Sara

AU - Jørgensen, Nis P.

AU - Sritharan, Sajitha S.

AU - Breining, Peter

AU - Jespersen, Søren

AU - Mortensen, Klaus L.

AU - Jensen, Mads L.

AU - Kolte, Lilian

AU - Frattari, Giacomo S.

AU - Larsen, Carsten S.

AU - Storgaard, Merete

AU - Nielsen, Lars P.

AU - Tolstrup, Martin

AU - Sædder, Eva A.

AU - Østergaard, Lars J.

AU - Ngo, Hien T.T.

AU - Jensen, Morten H.

AU - Højen, Jesper F.

AU - Kjolby, Mads

AU - Søgaard, Ole S.

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1016/j.eclinm.2021.100849

DO - 10.1016/j.eclinm.2021.100849

M3 - Journal article

C2 - 33903855

AN - SCOPUS:85106067590

VL - 35

JO - EClinicalMedicine

JF - EClinicalMedicine

SN - 2589-5370

M1 - 100849

ER -