This is a randomized controlled trial of the efficacy and safety evaluation of oral administration of Bromhexine hydrochloride for the prevention of SARS-CoV-2 infection and COVID-19 disease in medical personnel assisting patients with a new coronavirus disease
This study aims to evaluate the oral administration of Bromhexine hydrochloride for the
prevention of SARS-CoV-2 infection and COVID-19 disease in medical personnel assisting
patients with a new coronavirus disease. The aim of the study is to determine the preventive
role of this drug in the framework of reducing the incidence of coronavirus infection in risk
groups (medical personnel). Several studies show, that the acute respiratory syndrome
coronavirus SARS-CoV uses endosomal cysteine proteases cathepsin B and L (CatB/L) and the
transmembrane protease serine type 2 (TMPRSS2) for the priming of the viral S-protein. The
new coronavirus SARS-CoV-2 penetrates into alveolar epithelial type two cells through a
similar mechanism. In detail, viral S-protein binds to pneumocyte angiotensin-converting
enzyme 2 (ACE2) and then undergoes cleaving by TMPRSS2 in S1- and S2-subunits. This leads to
the release of a fusion peptide, which allows the virus to enter the cell via endocytosis.
Therefore, the protease TMPRSS2 can serve as a target for pharmacological agents to prevent
the penetration of the SARS-CoV-2 into the cell. Bromhexine blocks the TMPRSS2 ability to
activate a zymogen precursor of tissue plasminogen activator in vitro. Interestingly, TMPRSS2
is blocked by much lower concentrations then required to inactivate other proteases in the
cell culture. However, these data cannot be simply extended to the clinical practice: whether
the concentration of bromhexine in the lung tissue of properly treated patients would be
enough to prevent the virus entry through the TMPRSS2-inactivation remains unclear. A
randomized study in people at risk for coronavirus infection will clarify the role of
Bromhexine hydrochloride as a prevention of this disease.
Drug: Bromhexine Hydrochloride
Medical personnel at risk for COVID-19 infection will receive study medication for 14 days
Inclusion Criteria:
1. Age of 18 years or more;
2. Negative test (PCR) for SARS-CoV-2 infection;
3. The absence of clinical manifestations of a respiratory infection;
4. Contact with patients with laboratory and / or clinically confirmed SARS-CoV-2
infection;
5. Signed informed consent to participate in the study.
Exclusion Criteria:
1. Intolerance to Bromhexine hydrochloride;
2. Work out of contact with SARS-CoV-2 infection;
3. Non-compliance with the rules for the use of personal protective equipment when
working with SARS-CoV-2 infection (the rules for the use of personal protective
equipment in accordance with the recommendations of the Ministry of Health of Russia
and the internal orders of the Director General of Almazov NMRC, relevant to the dates
of research);
4. Pregnancy and the period of breastfeeding;
5. Other circumstances that the researcher considers inappropriate to participate in this
study
Almazov National Medical Research Centre
Saint Petersburg, Russian Federation
Evgeny Mikhaylov, MD, PhD, Study Director
Almazov National Medical Research Centre