Using BCG Vaccine to Protect Health Care Workers in the COVID-19 Pandemic

  • STATUS
    Recruiting
  • End date
    Aug 1, 2021
  • participants needed
    1500
  • sponsor
    Bandim Health Project
Updated on 27 January 2021

Summary

Background: The COVID-19 pandemic challenges the available hospital capacity, and this will be augmented by absenteeism of healthcare workers (HCW). HCW are at high risk, currently HCW constitute 20% of all the COVID-19 cases in Denmark. Strategies to prevent absenteeism of HCW are urgently needed.

Bacille Calmette-Gurin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other infections; significant reductions in morbidity and mortality have been reported, and a plausible immunological mechanism has been identified.

We hypothesize that BCG vaccination can reduce HCW absenteeism during the COVID-19 pandemic.

Primary objective: To reduce absenteeism among HCW with direct patient contacts during the COVID-19 epidemic. Secondary objective: To reduce the number of HCW that are infected with SARS-CoV-2 during the COVID-19 epidemic and to reduce the number of hospital admissions amongst HCW with direct patient contacts during the COVID-19 epidemic.

Study design: A multi-center randomized placebo controlled trial. Study population: 1500 HCW with direct patient contacts; defined as nurses, physicians and other medical staff working at emergency rooms and wards where COVID-infected patients are treated.

Intervention: Participants will be randomized 1:1 to intradermal administration of a standard dose of BCG vaccine or placebo (saline).

Main study parameters/endpoints: Primary endpoint: Number of days of (unplanned) absenteeism for any reason. Secondary endpoints: Number of days of (unplanned) absenteeism because of documented COVID infection. Cumulative incidence of hospital admissions.

Risk for participants and impact: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the potential beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of COVID infection.

Description

BACKGROUND Health-care workers face an elevated risk of exposure to - and infection with - SARS-CoV-2. It is imperative to ensure the safety, health and fitness of hospital personnel in order to safeguard continuous patient care. Strategies to prevent COVID-19 or to mitigate its clinical consequences are urgently needed.

Bacillus Calmette-Gurin (BCG) was developed as a vaccine against tuberculosis, but our group has shown that it can protect against death from other infections, it has what we have called non-specific effects (NSEs).[3] In clinical studies, BCG vaccination was associated with less child mortality, mainly as a result of reduced neonatal sepsis and respiratory infections. In a WHO-commissioned meta-analysis, BCG was associated with 42% (95%CI: 24-55%) lower child mortality.

NSEs of BCG are not limited to children. An Indonesian trial has shown that consecutive BCG vaccination for 3 months reduced the incidence of acute upper tract respiratory infections by 80% (95%CI=22-95%).

It has been recently demonstrated that the non-specific beneficial effects of BCG vaccination are due to epigenetic and metabolic reprogramming of innate immune cells, a process termed 'trained immunity'. E.g. among humans receiving yellow fever vaccine virus, those who had received BCG had - compared to placebo treated subjects - lower viral load, and improved anti-viral responses.

We hypothesize that BCG vaccination may induce (partial) protection against susceptibility to and/or severity of COVID-19. This study will evaluate the efficacy of BCG to improve the clinical course of COVID-19 and to prevent absenteeism.

Given the immediate threat of the COVID-19 epidemic the trial has been designed as a pragmatic study with a highly feasible primary endpoint, that can be continuously measured. We have therefore chosen unplanned absenteeism from work as primary outcome, in line with an ongoing clinical trial of BCG in the Netherlands.

OBJECTIVES Primary objective: To reduce absenteeism among HCW with direct patient contacts during the COVID-19 epidemic. Secondary objective: To reduce the number of HCW that are infected with SARS-CoV-2 during the COVID-19 epidemic and to reduce the number of hospital admissions amongst HCW with direct patient contacts during the COVID-19 epidemic.

HYPOTHESIS BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months.

METHODS

Study design and follow-up:

A multi-center randomized placebo-controlled trial.

STUDY POPULATION As the COVID-19 epidemic has already started in Denmark, our intention is to start as soon as possible. Recruitment of study participants will take place at participating hospitals, at departments were COVID-19 patients are treated and, thus, the risk of exposure to SARS-CoV-2 is high.

Participating hospitals Hospital PI Odense University Hospital Isik Somuncu Johansen Sygehus Lilleblt, Kolding Poul-Erik Kofoed Hvidovre Hospital Thomas Lars Benfield Nordsjllands Hospital Ellen Lkkegaard Aarhus University Hospital Christian Wejse Herning Hospital Lars Skov Dalgaard Sygehus Snderjylland Christian B. Mogensen

TREATMENT OF SUBJECTS Participants will be randomized 1:1 to receiving one intradermal BCG vaccine or placebo. Participants that are randomized in the active arm will receive a BCG vaccine (BCG-Denmark, AJ Vaccines). Placebo will be 0.1 ml sterile 0.9 % NaCl, which has a similar color as the resuspended BCG vaccine.

STUDY PROCEDURES Day 0: Participants fill in a short questionnaire regarding baseline characteristics. A blood sample will be drawn for subsequent testing for SARS-CoV-2 antibodies. Participants will be randomised to BCG or placebo in a 1:1 ratio. Randomisation will be done centrally using the REDCap tool with stratification per hospital and by age groups (+/- 45 years of age) in blocks of 8.

Participants will be blinded to treatment. The physicians administering the BCG vaccine or placebo will not be blinded. In case of serious adverse events, the participant can be unblinded after consultation with the coordinating PI or sponsor.

The end of the trial is defined as whichever comes latest: the last patient's last registration in the online data collection, or 180 days.

Day 0 till end of trial (weekly): Short electronic questionnaire regarding work absenteeism, symptoms and side effects through REDCap. In case a participant reports acute respiratory symptoms indicating COVID-19, he or she will be tested depending on test availability.

End of trial: Participants are asked to fill in a final questionnaire. A blood sample will be drawn for subsequent testing for SARS-CoV-2 antibodies.

STATISTICAL ANALYSIS All analyses will be performed from the intention-to-treat principle.

Primary study parameter:

The primary endpoint will be analysed as counts per week (i.e. multiple observations per subject) using a Bayesian negative binomial regression. Similar regression models will be used for secondary endpoints: Number of days of unplanned absenteeism because of documented COVID; number of days of self-reported fever. Documented COVID, death for any reason, death due to documented COVID, cumulative incidence of Intensive Care Admission for any reason, cumulative incidence of Intensive Care Admission due to documented COVID, cumulative incidence of Hospital Admission for any reason, cumulative incidence of Hospital Admission due to documented COVID will be analysed in Cox proportional hazards models.

When applicable (i.e. in the event that one or more participants have died during the follow-up period) a competing events analysis will be performed in addition.

Interim analysis Every month, an interim analysis will be conducted by the independent statistician of the trial. The parallel Dutch trial will enable combined analysis that will strengthen the conclusions and increase the power to analyse the secondary outcomes and more rare outcomes as intensive hospitalization.

ETHICAL CONSIDERATIONS The study has ben approved by the Ethics Committee and by the Danish Medicines Agency.

Details
Condition Morbidity, Absenteeism, Frequency, Heterologous Immunity, *COVID-19, Covid-19, Non-specific Effects of Vaccines, Non-specific Effects of Vaccines, Non-specific Effects of Vaccines, Non-specific Effects of Vaccines
Treatment Saline, BCG-Denmark
Clinical Study IdentifierNCT04373291
SponsorBandim Health Project
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Heterologous Immunity or Frequency or Non-specific Effects of Vaccines or *COVID-19 or Absenteeism or Morbidity or Covid-19?
Do you have any of these conditions: Non-specific Effects of Vaccines or Frequency or *COVID-19 or Absenteeism or Morbidity or Heterologous Immunity or Covid-19?
Do you have any of these conditions: Frequency or Covid-19 or Non-specific Effects of Vaccines or *COVID-19 or Morbidity or Heterologous Immunity or Absenteeism?
Do you have any of these conditions: Absenteeism or Non-specific Effects of Vaccines or Morbidity or Frequency or Covid-19 or Heterologous Immunity or *COVID-19?
In order to be eligible to participate in this study, a subject must meet the
following
criteria
Adult (18 years)
Hospital personnel caring for patients with COVID-19

Exclusion Criteria

Known allergy to (components of) the BCG vaccine or serious adverse events to prior BCG administration
Known active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species
Previous M. tuberculosis infection
Previous confirmed COVID-19 infection
Fever (>38 C) within the past 24 hours
Suspicion of active viral or bacterial infection
Pregnancy
Severely immunocompromised subjects (This exclusion category comprises a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) subjects with solid organ transplantation; c) subjects with bone marrow transplantation; d) subjects under chemotherapy; e) subjects with primary immunodeficiency; f) treatment with any anti-cytokine therapies. g) treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months)
Active solid or non-solid malignancy or lymphoma within the prior two years
Direct involvement in the design or the execution of the BCG-DENMARK-COVID study
Employed to the hospital < 22 hours per week
Not in possession of a smartphone/tablet
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note