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

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

doi:10.1016/j.eclinm.2021.100849

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

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 CajanderNis 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^*

^*Corresponding author for this work

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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. 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.

Original language	English
Article number	100849
Journal	EClinicalMedicine
Volume	35
ISSN	2589-5370
DOIs	https://doi.org/10.1016/j.eclinm.2021.100849
Publication status	Published - May 2021

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Gunst, J. D., Staerke, N. B., Pahus, M. H., Kristensen, L. H., Bodilsen, J., Lohse, N., Dalgaard, L. S., Brønnum, D., Fröbert, O., Hønge, B., Johansen, I. S., Monrad, I., Erikstrup, C., Rosendal, R., Vilstrup, E., Mariager, T., Bove, D. G., Offersen, R., Shakar, S., ... Søgaard, O. S. (2021). Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial. EClinicalMedicine, 35, Article 100849. https://doi.org/10.1016/j.eclinm.2021.100849

@article{a311d5682cf844fb91a79c7ac33a916c,

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

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. 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.",

author = "Gunst, {Jesper D.} and Staerke, {Nina B.} and Pahus, {Marie H.} and Kristensen, {Lena H.} and Jacob Bodilsen and Nicolai Lohse and Dalgaard, {Lars S.} and Dorthe Br{\o}nnum and Ole Fr{\"o}bert and Bo H{\o}nge and Johansen, {Isik S.} and Ida Monrad and Christian Erikstrup and Regitze Rosendal and Emil Vilstrup and Theis Mariager and Bove, {Dorthe G.} and Rasmus Offersen and Shakil Shakar and Sara Cajander and J{\o}rgensen, {Nis P.} and Sritharan, {Sajitha S.} and Peter Breining and S{\o}ren Jespersen and Mortensen, {Klaus L.} and Jensen, {Mads L.} and Lilian Kolte and Frattari, {Giacomo S.} and Larsen, {Carsten S.} and Merete Storgaard and Nielsen, {Lars P.} and Martin Tolstrup and S{\ae}dder, {Eva A.} and {\O}stergaard, {Lars J.} and Ngo, {Hien T.T.} and Jensen, {Morten H.} and H{\o}jen, {Jesper F.} and Mads Kjolby and S{\o}gaard, {Ole S.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = may,

doi = "10.1016/j.eclinm.2021.100849",

language = "English",

volume = "35",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "The Lancet Publishing Group",

}

Gunst, JD , Staerke, NB , Pahus, MH, Kristensen, LH, Bodilsen, J, Lohse, N, Dalgaard, LS, Brønnum, D, Fröbert, O , Hønge, B, Johansen, IS, Monrad, I , Erikstrup, C, Rosendal, R, Vilstrup, E, Mariager, T, Bove, DG, Offersen, R, Shakar, S, Cajander, S, Jørgensen, NP, Sritharan, SS, Breining, P, Jespersen, S, Mortensen, KL, Jensen, ML, Kolte, L, Frattari, GS, Larsen, CS , Storgaard, M, Nielsen, LP, Tolstrup, M , Sædder, EA , Østergaard, LJ, Ngo, HTT, Jensen, MH, Højen, JF, Kjolby, M & Søgaard, OS 2021, 'Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.', EClinicalMedicine, vol. 35, 100849. https://doi.org/10.1016/j.eclinm.2021.100849

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial. / Gunst, Jesper D.; Staerke, Nina B.; Pahus, Marie H. et al.
In: EClinicalMedicine, Vol. 35, 100849, 05.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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 S.

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.

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 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.

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

AN - SCOPUS:85106067590

SN - 2589-5370

VL - 35

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 100849

ER -

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

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