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Performance Evaluation of BCG Vaccination in Healthcare Personnel to Reduce the Severity of COVID-19 Infection.

U

Universidad de Antioquia

Status and phase

Withdrawn
Phase 3

Conditions

COVID-19

Treatments

Biological: vaccine BCG
Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT04362124
PEC03_2020

Details and patient eligibility

About

Until the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view.

Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses.

Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them.

For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death.

In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.

Full description

Problem Statement

To date, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases (1). Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. This theory has been gathering momentum in other latitudes, demonstrating how the asymptomatic infected individuals are responsible for spreading the infection .

Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question, an extensive literature search of factors that differentiate Europeans from Latin Americans was carried out. Finding, in addition to genetic factors specific to race, differences in the number of ACEI receptors (binding site of the coronavirus to the alveolus), and differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe (3). This last finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses (4,5).

Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations.

Currently, there are no vaccines or proven preventive interventions available to protect health-care workers. However, researchers from Germany, the Netherlands, Australia, and France are working on a clinical trial with an unorthodox approach to combat this new virus. This research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. Initially, studies in these four countries will be carried out on doctors and nurses, since they are the ones with a higher risk of becoming infected compared to the general population.

Currently, the available evidence supports the hypothesis that BCG vaccination has beneficial heterologous effects against viral, bacterial, and fungal infections. The basis of these effects has been little explored in humans; however, this knowledge opens the door to future research to explore the effect of "trained immunity" associated with this vaccine, both for diseases in hosts with immunological disorders, and for autoinflammatory diseases, in which there is an inappropriate activation of inflammation (21). All of the findings described have considerable potential to aid in the design of new therapeutic strategies, such as the use of old and new vaccines that combine classical immune memory, and the activation of innate immunity by "trained immunity," for prevention and treatment of infections, and modulation of exaggerated inflammation in autoinflammatory diseases.

A multicenter, double-blind, randomized, phase III clinical trial will be carried out. 1000 healthy healthcare workers (doctors, nurses, and nursing assistants) with a negative test for COVID-19 and asymptomatic for the disease will be randomly assigned to receive one dose of BGC vaccine or placebo (saline solution). Volunteers will be followed for one year.

Hypothesis Healthcare workers who have negative SARS-Cov-2 serology and who receive the BCG vaccine, have a better clinical outcome if they become infected with COVID-19, in terms of not getting sick, requiring hospitalization or dying, than those who do not receive the vaccine.

Objectives

Overall Objective

Evaluate the performance of BCG vaccination in reducing the severity of SARS-COV-2 infection compared to the placebo, in healthcare personnel from Medellín, Colombia.

. Specific Objectives

  • Determine if there are differences in the clinical outcome in terms of not getting sick, requiring hospitalization, or dying in both treatment groups.
  • Estimate previous exposure of healthcare personnel to SARS-Cov-2 by conducting rapid tests that measure IgG and IgM immunity.
  • Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination in an adult population.
  • Estimate SARS-Cov-2 infection in healthcare personnel at the end of the study, by performing rapid tests that measure IgG and IgM immunity.

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

  • Men and women
  • Between ≥18 and ≤ 65 years old
  • Healthcare workers (doctors, nurses and nursing assistants) from clinics and hospitals in Medellín, who are directly involved in the care of patients with COVID-19
  • A negative test for COVID-19 and being asymptomatic at baseline
  • Are able and willing to give signed informed consent (Subjects whom the investigator believes are able to understand and are willing to comply with the requirements of the protocol)

Exclusion Criteria

  • Have a previous diagnosis (probable or confirmed) of COVID-19
  • Immunosuppression (pharmacological or clinical)
  • Are taking immunosuppressive medications
  • Pregnant or lactating women; or women of childbearing age who do not agree to take contraceptives during the month following vaccination.
  • Have received any live or replicative vaccine one month before the time of screening.
  • Permanent teleworking activity.
  • History of active tuberculosis
  • Currently are receiving Hydroxychloroquine, Chloroquine, Lopinavir/ritonavir, Tocilizumab, or Azithromycin.
  • Known or suspected history of hypersensitivity to vaccines.
  • Patients who do not wish to attend or who cannot keep up with the follow-up visits.

Trial design

Primary purpose

Supportive Care

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

0 participants in 2 patient groups, including a placebo group

vaccine BCG
Experimental group
Description:
A single dose intradermal application of 0.1 ml of between 1 x 105 to 33 x 105 CFU of BCG, in the deltoid of the non-dominant arm. Follow-up of the participant up to day 360. The frequency and intensity of possible Adverse Events, reactions, and symptoms that appear, and other reactions stipulated in the protocol will be documented in the subject's diary.
Treatment:
Biological: vaccine BCG
Placebo
Placebo Comparator group
Description:
A single dose intradermal application of 0.1ml of normal saline solution, in the deltoid of the non-dominant arm. Follow-up of the participant up to day 360. The frequency and intensity of possible Adverse Events, reactions, and symptoms that appear, and other reactions stipulated in the protocol will be documented in the subject's diary.
Treatment:
Other: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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