Increased Risk of SARS-CoV-2 Infection
Conditions
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.
Interventions
DRUGBromhexine Hydrochloride
Medical personnel at risk for COVID-19 infection will receive study medication for 14 days
Sponsors
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Negative Polymerase Chain Reaction (PCR) | 4 weeks after randomization | Number of Participants with Negative PCR of SARS-CoV-2 and The Absence of Clinical Manifestations of COVID-19 Infection in individuals taking Bromhexine hydrochloride 4 weeks after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Asymptomatic SARS-CoV-2 Infection | 14 days after last contact | Number of Participants with Asymptomatic SARS-CoV-2 Infection |
| Number of Participants With Mild, Moderate and Severe COVID-19 Disease | 14 days after last contact | number of participants with mild, moderate and severe COVID-19 disease |
| Number of Participants With Adverse Events | 14 days after last contact | Number of Participants with Adverse Events |
Countries
Russia
Participant flow
Recruitment details
Recruitment was performed via the institution's electronic communication system and via personal contacts with healthcare providers. Following a general notification via an institutional electronic system, one hundred and fifty healthcare providers were contacted personally and 50 persons were included.
Pre-assignment details
No subjects were excluded from the study before assignment to groups.
Participants by arm
| Arm | Count |
|---|---|
| Bromhexine Hydrochloride Group medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days | 25 |
| Control Group medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Bromhexine Hydrochloride Group | Total | Control Group |
|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 6.9 | 40.6 years STANDARD_DEVIATION 7.2 | 39.5 years STANDARD_DEVIATION 8.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 50 Participants | 25 Participants |
| Region of Enrollment Russia | 25 participants | 50 participants | 25 participants |
| Sex: Female, Male Female | 14 Participants | 29 Participants | 15 Participants |
| Sex: Female, Male Male | 11 Participants | 21 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 2 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Negative Polymerase Chain Reaction (PCR)
Number of Participants with Negative PCR of SARS-CoV-2 and The Absence of Clinical Manifestations of COVID-19 Infection in individuals taking Bromhexine hydrochloride 4 weeks after randomization.
Time frame: 4 weeks after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Negative Polymerase Chain Reaction (PCR) | 2 Participants |
| Control Group | Negative Polymerase Chain Reaction (PCR) | 7 Participants |
Secondary
Number of Participants With Adverse Events
Number of Participants with Adverse Events
Time frame: 14 days after last contact
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participants With Adverse Events | 2 Participants |
| Control Group | Number of Participants With Adverse Events | 0 Participants |
Secondary
Number of Participants With Asymptomatic SARS-CoV-2 Infection
Number of Participants with Asymptomatic SARS-CoV-2 Infection
Time frame: 14 days after last contact
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participants With Asymptomatic SARS-CoV-2 Infection | 2 Participants |
| Control Group | Number of Participants With Asymptomatic SARS-CoV-2 Infection | 2 Participants |
Secondary
Number of Participants With Mild, Moderate and Severe COVID-19 Disease
number of participants with mild, moderate and severe COVID-19 disease
Time frame: 14 days after last contact
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participants With Mild, Moderate and Severe COVID-19 Disease | 0 Participants |
| Control Group | Number of Participants With Mild, Moderate and Severe COVID-19 Disease | 5 Participants |