Clinical trial NCT04405999: Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease
Official title: Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Increased Risk of SARS-CoV-2 Infection
Lead sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Sponsor class: OTHER
First posted: 2020-05-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Negative Polymerase Chain Reaction (PCR)
timeFrame: 4 weeks after randomization
Secondary outcomes:
measure: Number of Participants With Asymptomatic SARS-CoV-2 Infection
timeFrame: 14 days after last contact
measure: Number of Participants With Mild, Moderate and Severe COVID-19 Disease
timeFrame: 14 days after last contact
measure: Number of Participants With Adverse Events
timeFrame: 14 days after last contact
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
Study officials:
affiliation: Almazov National Medical Research Centre
name: Evgeny Mikhaylov, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Mikhaylov EN, Lyubimtseva TA, Vakhrushev AD, Stepanov D, Lebedev DS, Vasilieva EY, Konradi AO, Shlyakhto EV. Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study. Interdiscip Perspect Infect Dis. 2022 Jan 29;2022:4693121. doi: 10.1155/2022/4693121. eCollection 2022.