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.; Kristensen, Lena H.; Bodilsen, Jacob; Lohse, Nicolai; Dalgaard, Lars S.; Brønnum, Dorthe; Fröbert, Ole; Hønge, Bo; Johansen, Isik S.; Monrad, Ida; Erikstrup, Christian; Rosendal, Regitze; Vilstrup, Emil; Mariager, Theis; Bove, Dorthe G.; Offersen, Rasmus; Shakar, Shakil; Cajander, Sara; Jørgensen, Nis P.; Sritharan, Sajitha S.; Breining, Peter; Jespersen, Søren; Mortensen, Klaus L.; Jensen, Mads L.; Kolte, Lilian; Frattari, Giacomo S.; Larsen, Carsten S.; Storgaard, Merete; Nielsen, Lars P.; Tolstrup, Martin; Sædder, Eva A.; Østergaard, Lars J.; Ngo, Hien T.T.; Jensen, Morten H.; Højen, Jesper F.; Kjolby, Mads; Søgaard, Ole S.

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(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.