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

• ClinicalTrials.gov Identifier: NCT04405999
• Recruitment Status: Completed
• First Posted: May 28, 2020
• Results First Posted: April 13, 2022
• Last Update Posted: April 13, 2022
• Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Information provided by (Responsible Party): Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Tracking Information

• First Submitted Date: May 18, 2020
• First Posted Date: May 28, 2020
• Results First Submitted Date: March 21, 2022
• Results First Posted Date: April 13, 2022
• Last Update Posted Date: April 13, 2022
• Actual Study Start Date: May 14, 2020
• Actual Primary Completion Date: August 9, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2022)

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.

Original Primary Outcome Measures (submitted: May 26, 2020)

Polymerase chain reaction (PCR) [ Time Frame: 4 weeks after randomization ]

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.

Current Secondary Outcome Measures (submitted: April 11, 2022)

• Number of Participants With Asymptomatic SARS-CoV-2 Infection [ Time Frame: 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 [ Time Frame: 14 days after last contact ]
  number of participants with mild, moderate and severe COVID-19 disease
• Number of Participants With Adverse Events [ Time Frame: 14 days after last contact ]
  Number of Participants with Adverse Events

Original Secondary Outcome Measures (submitted: May 26, 2020)

• Time to symptoms [ Time Frame: 14 days after last contact ]
  Time to clinical symptoms of a respiratory infection with positive PCR SARS-CoV-2
• Time to positive PCR [ Time Frame: 14 days after last contact ]
  Time to detect positive SARS-CoV-2 PCR
• Number of cases [ Time Frame: 14 days after last contact ]
  The number of asymptomatic cases of SARS-CoV-2 infection
• Case severity [ Time Frame: 14 days after last contact ]
  The number of mild, moderate and severe forms of the disease COVID-19 with Bromhexine hydrochloride
• Drug tolerance [ Time Frame: 14 days after last contact ]
  Evaluation of adverse events

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Increased Risk of SARS-CoV-2 Infection

Intervention

Drug: Bromhexine Hydrochloride

Medical personnel at risk for COVID-19 infection will receive study medication for 14 days

Study Arms

• Experimental: Bromhexine hydrochloride Group
  medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride
  Intervention: Drug: Bromhexine Hydrochloride
• No Intervention: Control Group
  medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 2, 2020): 50
• Original Estimated Enrollment (submitted: May 26, 2020): 140
• Actual Study Completion Date: August 31, 2020
• Actual Primary Completion Date: August 9, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT04405999
• Other Study ID Numbers: 05-20-02-С
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Evgeny Mikhaylov, MD, PhD; Almazov National Medical Research Centre

• PRS Account: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Verification Date: March 2022