Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease

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

Study Overview

• Status: Completed
• Conditions: Increased Risk of SARS-CoV-2 Infection
• Intervention / Treatment: Drug: Bromhexine Hydrochloride

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197341
    • Almazov National Medical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bromhexine hydrochloride Group; medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride	Drug: Bromhexine Hydrochloride; Medical personnel at risk for COVID-19 infection will receive study medication for 14 days
No Intervention: Control Group; medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Asymptomatic SARS-CoV-2 Infection	Number of Participants with Asymptomatic SARS-CoV-2 Infection	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	14 days after last contact
Number of Participants With Adverse Events	Number of Participants with Adverse Events	14 days after last contact

Collaborators and Investigators

• Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Investigators: Study Director: Evgeny Mikhaylov, MD, PhD, Almazov National Medical Research Centre

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2020
• Primary Completion (Actual): August 9, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases; Respiratory System Agents; Expectorants; Bromhexine
• Other Study ID Numbers: 05-20-02-С

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No