Increased Risk of SARS-CoV-2 InfectionPhase 4NCT04405999
Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease
A Phase 4 study testing Bromhexine Hydrochloride in people with Increased Risk of SARS-CoV-2 Infection, run by Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health at 1 site in Russia.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Increased Risk of SARS-CoV-2 Infection
- What is being tested?
- Bromhexine Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteRussia
- Study dates
- 14 May 2020to 31 Aug 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age of 18 years or more;
- Negative test (PCR) for SARS-CoV-2 infection;
- The absence of clinical manifestations of a respiratory infection;
- Contact with patients with laboratory and / or clinically confirmed SARS-CoV-2 infection;
- Signed informed consent to participate in the study.
Who cannot join
- Intolerance to Bromhexine hydrochloride;
- Work out of contact with SARS-CoV-2 infection;
- 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);
- Pregnancy and the period of breastfeeding;
- Other circumstances that the researcher considers inappropriate to participate in this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease: a Randomised Controlled Trial
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
Read the 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.
- Conditions
- Increased Risk of SARS-CoV-2 Infection
- Being tested
- Bromhexine Hydrochloride
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bromhexine HydrochlorideDrug
Medical personnel at risk for COVID-19 infection will receive study medication for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Bromhexine hydrochloride Group | Experimental | medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride Receives: Drug: Bromhexine Hydrochloride |
| Control Group | No intervention | medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks after randomization
Secondary outcomes (3)
Number of Participants With Asymptomatic SARS-CoV-2 Infection
Number of Participants with Asymptomatic SARS-CoV-2 Infection
Measured: 14 days after last contact
Number of Participants With Mild, Moderate and Severe COVID-19 Disease
number of participants with mild, moderate and severe COVID-19 disease
Measured: 14 days after last contact
Number of Participants With Adverse Events
Number of Participants with Adverse Events
Measured: 14 days after last contact
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2020
- Study start14 May 2020
- Primary completion9 Aug 2020
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Increased Risk of SARS-CoV-2 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Evgeny Mikhaylov, MD, PhD, Study director, Almazov National Medical Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04405999
- Sponsor's protocol ID
- 05-20-02-С
- Status last verified
- Mar 2022
- First submitted
- 18 May 2020
- Last updated
- 13 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35103059
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease: a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT04405999
- Acronym / sponsor ID
- 05-20-02-С
- Conditions
- Increased Risk of SARS-CoV-2 Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of HealthUniversity, hospital or other
- Study start
- 14 May 2020 (actual)
- Primary completion
- 9 Aug 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 28 May 2020 (actual)
- Results
- Posted 13 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bromhexine hydrochloride Group | Experimental | Drug: Bromhexine Hydrochloridemedical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride |
| Control Group | No intervention | –medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age of 18 years or more;
- Negative test (PCR) for SARS-CoV-2 infection;
- The absence of clinical manifestations of a respiratory infection;
- Contact with patients with laboratory and / or clinically confirmed SARS-CoV-2 infection;
- Signed informed consent to participate in the study.
Key exclusion criteria (5 listed)
- Intolerance to Bromhexine hydrochloride;
- Work out of contact with SARS-CoV-2 infection;
- 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);
- Pregnancy and the period of breastfeeding;
- Other circumstances that the researcher considers inappropriate to participate in this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bromhexine HydrochlorideMedical personnel at risk for COVID-19 infection will receive study medication for 14 days | Drug | Bromhexine hydrochloride Group |
Primary outcome
Negative Polymerase Chain Reaction (PCR)
Time frame: 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.
3 secondary outcomes
Number of Participants With Asymptomatic SARS-CoV-2 Infection
Time frame: 14 days after last contact
Number of Participants With Mild, Moderate and Severe COVID-19 Disease
Time frame: 14 days after last contact
Number of Participants With Adverse Events
Time frame: 14 days after last contact
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35103059Mikhaylov 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.
- Individual participant dataSharing planned: No
Related trials for Increased Risk of SARS-CoV-2 Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evgeny Mikhaylov, MD, PhD study director
Almazov National Medical Research Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bromhexine Hydrochloride in people with Increased Risk of SARS-CoV-2 Infection, run by Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Negative Polymerase Chain Reaction (PCR) (time frame: 4 weeks after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04405999, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2022.