Prevention, Efficacy and Safety of BCG Vaccine in COVID-19 Among Healthcare Workers

Hospital Universitario Dr. Jose E. Gonzalez

Status and phase

Unknown

Phase 3

Conditions

COVID-19

Corona Virus Infection

SARS-CoV2

BCG

Treatments

Biological: BCG vaccine

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT04461379

EN20-00011

Details and patient eligibility

About

In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.

Full description

The study design is a randomized, double-blinded, placebo-controlled clinical trial.

Age stratified randomization (<45 years and> 45 years) was performed using permuted blocks with allocation concealment.

The sample size is 908 patients. 454 patients in each stratum (227 with placebo and 227 with BCG vaccine).

Eligible participants will be healthcare professionals over 18 years of age who are in contact with patients with COVID-19, with negative IgG and IgM antibodies results for SARS-CoV-2 prior to their inclusion and sign the informed consent. After signing the informed consent, the participants will be randomized 1:1 to the intervention group (BCG vaccine) or control (placebo), a medical history will be performed, and a blood plasma sample will be obtained to determine specific antibodies against SARS-CoV-2.

The patients will be followed up for 6 months after the application of the vaccine, they will be contacted by phone every two weeks in order to identify the adverse effects of the vaccine (30 days after the application) as well as to identify symptoms of COVID-19, in addition, follow-up visits will be carried out at the third and sixth months, in each of these visits a blood plasma sample will be obtained and IgG and IgM antibodies will be measured.

Statistical Analysis Type: By intention to treatment

Enrollment

908 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Health workers who are working onsite in patients' areas with COVID-19
Age > 18 years
Negative specific IgG and IgM antibodies test result for SARS CoV-2 before the enrollment.
Provide a signed and dated informed consent form

Exclusion criteria

Age <18 years
Positive test for specific antibodies IgG and IgM antibodies result for SARS Cov-2
Primary or secondary immunosuppression
Use of immunosuppression drugs, use of hydroxychloroquine, cloroquine, Azithromycin, Lopinavir/ritonavir, Ivermectin or any other drug used to treat patients COVID-19 before the enrollment.
Chemotherapy treatment
Presence of antibodies IgA, IgM, IgG against SARS-CoV-2
Pregnancy or breastfeeding
Missing informed consent form
Fever > 38° in the previous 24 hours
Any BCG vaccine contraindication
History of previous allergy to the components of the vaccine
Already part of any other trial
Previous or active tuberculosis (TB) disease
Another vaccine administrated 4 months before the start of the trial.
Any underlying history of malignancy or lymphoma.
Actual treatment with steroids
Absence of more than 1 month from the hospital, from the study period.