Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.
Jesper Damsgaard Gunst, Nina Breinholt Stærke, Marie H. Pahus, Lena Hagelskjær Kristensen, Jacob Bodilsen, Nicolai Lohse, Lars Dalgaard, Dorthe Brønnum, Ole Fröbert, Bo Langhoff Hønge, Işık Somuncu Johansen, Ida Monrad, Christian Erikstrup, Regitze Rosendal, Emil Vilstrup, Theis Mariager, Dorthe Gaby Bové, Rasmus Offersen, Shakil Shakar, Sara Cajander, Nis Pedersen Jørgensen, Sajitha Sophia Sritharan, Peter Breining, S.K. Jespersen, Klaus Leth Mortensen, Mads Langballe Jensen, Lilian Kolte, Giacomo S. Frattari, Carsten Schade Larsen, Merete Storgaard, Lars Peter Nielsen, Martin Tolstrup, Eva Aggerholm Sædder, Lars Østergaard, Hien T. T. Ngo, Morten Hasselstrøm Jensen, Jesper Falkesgaard Højen, Mads Kjølby, Ole S. Søgaard
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 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.