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 Damsgaard
AU - Stærke, Nina Breinholt
AU - Pahus, Marie Høst
AU - Kristensen, Lena Hagelskjær
AU - Bodilsen, Jacob
AU - Lohse, Nicolai
AU - Dalgaard, Lars Skov
AU - Brønnum, Dorthe
AU - Frøbert, Ole
AU - Hønge, Bo
AU - Johansen, Isik Somuncu
AU - Hansen, Ida Preetzmann Monrad
AU - Erikstrup, Christian
AU - Rosendal, Regitze
AU - Vilstrup, Emil
AU - Mariager, Theis
AU - Bove, Dorthe G.
AU - Offersen, Rasmus
AU - Shakar, Shakil Ahmad
AU - Cajander, Sara
AU - Jørgensen, Nis Pedersen
AU - Sritharan, Sajitha Sophia
AU - Breining, Peter
AU - Jespersen, Søren
AU - Mortensen, Klaus Leth
AU - Jensen, Mads L.
AU - Kolte, Lilian Østergaard
AU - Frattari, Giamoco S.
AU - Larsen, Carsten S
AU - Storgaard, Merete
AU - Nielsen, Lars P
AU - Tolstrup, Martin
AU - Sædder, Eva Aggerholm
AU - Østergaard, Lars
AU - Ngo, Hien T. T.
AU - Jensen, Morten Hasselstrøm
AU - Højen, Jesper Falkesgaard
AU - Kjolby, Mads
AU - Søgaard, Ole S.
N1 - © 2021 The Authors.
PY - 2021/5
Y1 - 2021/5
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 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=85106067590&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2021.100849
DO - 10.1016/j.eclinm.2021.100849
M3 - Journal article
C2 - 33903855
SN - 2589-5370
VL - 35
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 100849
ER -