tetano
Editor, Senior Moderator
EClinicalMedicine
. 2021 Apr 22;100849.
doi: 10.1016/j.eclinm.2021.100849. Online ahead of print.
Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
Jesper D Gunst[SUP] 1 [/SUP], Nina B Staerke[SUP] 1 [/SUP], Marie H Pahus[SUP] 2 [/SUP], Lena H Kristensen[SUP] 3 [/SUP], Jacob Bodilsen[SUP] 4 [/SUP], Nicolai Lohse[SUP] 5 6 [/SUP], Lars S Dalgaard[SUP] 7 [/SUP], Dorthe Br?nnum[SUP] 8 [/SUP], Ole Fr?bert[SUP] 9 [/SUP], Bo H?nge[SUP] 1 10 [/SUP], Isik S Johansen[SUP] 11 [/SUP], Ida Monrad[SUP] 1 [/SUP], Christian Erikstrup[SUP] 2 12 [/SUP], Regitze Rosendal[SUP] 12 [/SUP], Emil Vilstrup[SUP] 3 [/SUP], Theis Mariager[SUP] 4 [/SUP], Dorthe G Bove[SUP] 5 [/SUP], Rasmus Offersen[SUP] 7 [/SUP], Shakil Shakar[SUP] 13 14 [/SUP], Sara Cajander[SUP] 15 [/SUP], Nis P J?rgensen[SUP] 1 10 [/SUP], Sajitha S Sritharan[SUP] 3 [/SUP], Peter Breining[SUP] 16 [/SUP], S?ren Jespersen[SUP] 5 [/SUP], Klaus L Mortensen[SUP] 7 [/SUP], Mads L Jensen[SUP] 3 [/SUP], Lilian Kolte[SUP] 17 [/SUP], Giacomo S Frattari[SUP] 1 [/SUP], Carsten S Larsen[SUP] 1 [/SUP], Merete Storgaard[SUP] 1 [/SUP], Lars P Nielsen[SUP] 16 18 [/SUP], Martin Tolstrup[SUP] 1 2 [/SUP], Eva A S?dder[SUP] 16 18 [/SUP], Lars J ?stergaard[SUP] 1 2 [/SUP], Hien T T Ngo[SUP] 1 [/SUP], Morten H Jensen[SUP] 19 20 [/SUP], Jesper F H?jen[SUP] 1 [/SUP], Mads Kjolby[SUP] 16 21 22 23 [/SUP], Ole S S?gaard[SUP] 1 2 [/SUP]
Affiliations
Abstract
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 log[SUB]10[/SUB] copies/mL (p <0?05) and -0?82 log[SUB]10[/SUB] 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.
. 2021 Apr 22;100849.
doi: 10.1016/j.eclinm.2021.100849. Online ahead of print.
Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
Jesper D Gunst[SUP] 1 [/SUP], Nina B Staerke[SUP] 1 [/SUP], Marie H Pahus[SUP] 2 [/SUP], Lena H Kristensen[SUP] 3 [/SUP], Jacob Bodilsen[SUP] 4 [/SUP], Nicolai Lohse[SUP] 5 6 [/SUP], Lars S Dalgaard[SUP] 7 [/SUP], Dorthe Br?nnum[SUP] 8 [/SUP], Ole Fr?bert[SUP] 9 [/SUP], Bo H?nge[SUP] 1 10 [/SUP], Isik S Johansen[SUP] 11 [/SUP], Ida Monrad[SUP] 1 [/SUP], Christian Erikstrup[SUP] 2 12 [/SUP], Regitze Rosendal[SUP] 12 [/SUP], Emil Vilstrup[SUP] 3 [/SUP], Theis Mariager[SUP] 4 [/SUP], Dorthe G Bove[SUP] 5 [/SUP], Rasmus Offersen[SUP] 7 [/SUP], Shakil Shakar[SUP] 13 14 [/SUP], Sara Cajander[SUP] 15 [/SUP], Nis P J?rgensen[SUP] 1 10 [/SUP], Sajitha S Sritharan[SUP] 3 [/SUP], Peter Breining[SUP] 16 [/SUP], S?ren Jespersen[SUP] 5 [/SUP], Klaus L Mortensen[SUP] 7 [/SUP], Mads L Jensen[SUP] 3 [/SUP], Lilian Kolte[SUP] 17 [/SUP], Giacomo S Frattari[SUP] 1 [/SUP], Carsten S Larsen[SUP] 1 [/SUP], Merete Storgaard[SUP] 1 [/SUP], Lars P Nielsen[SUP] 16 18 [/SUP], Martin Tolstrup[SUP] 1 2 [/SUP], Eva A S?dder[SUP] 16 18 [/SUP], Lars J ?stergaard[SUP] 1 2 [/SUP], Hien T T Ngo[SUP] 1 [/SUP], Morten H Jensen[SUP] 19 20 [/SUP], Jesper F H?jen[SUP] 1 [/SUP], Mads Kjolby[SUP] 16 21 22 23 [/SUP], Ole S S?gaard[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33903855
- PMCID: PMC8060682
- DOI: 10.1016/j.eclinm.2021.100849
Abstract
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 log[SUB]10[/SUB] copies/mL (p <0?05) and -0?82 log[SUB]10[/SUB] 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.