Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers

Study Overview
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Brief Summary
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The disease promoted by coronavirus (COVID-19) is caused by Severe Acute Respiratory Syndrome (SARS) caused by Coronavirus type 2 (CoV2), being the first cases identified in December 2019 in China after exposure to the animal market in Wuhan city, China. From the first case to the present day, the COVID-19 epidemic has been identified in 185 countries, with the notification of 2,666,154 cases and 186,144 deaths. In Brazil, more than 45,757 cases and 2,906 confirmed deaths by COVID-19 have been confirmed (Visualized on Apr 23 2020). In our country, to date, testing for COVID-19 occurs only in severe cases and few centers offer the service to health care workers, a population at high risk of infection. BCG is a vaccine produced from a live attenuated strain derived from a Mycobacterium bovis isolate and is widely used worldwide as a tuberculosis (TB) vaccine, but there are studies demonstrating non-specific immunotherapeutic mechanisms of this vaccine that signal a possible relationship with the lowest morbidity and mortality associated with COVID-19 infections worldwide. The present study aims to analyze the role of BCG in the prevention of SARS-CoV-2 infection and also in the occurrence of severe forms of COVID-19 in addition to evaluating the immune response mediated by this vaccine in voluntary health care workers.

Detailed Description
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Study detailed description can be seen on the protocol attached.

Official Title
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Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers

Conditions
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COVID 19 Vaccine

Intervention / Treatment
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* Biological: BCG vaccine
* Biological: 0.9% sodium chloride (NaCl) saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged 18 ≥, male or female, not infected with SARS-CoV-2 Agreement to participate in the study by signing the Free Informed Consent (FIC) Not being pregnant (in case of women able to become pregnant) Have not received a specific vaccine against COVID-19 or, if vaccinated against SARS-CoV-2, have received the complete immunization schedule only with vaccines approved by ANVISA and implemented by the National Immunization Program, (including the second dose) within a minimum of 15 days prior to the date of inclusion in the study If the participant have not received a specific vaccine against COVID-19 approved by ANVISA, be aware and agree to be able to receive them only 15 days after the intervention proposed in this study Exclusion Criteria: Professionals with a history of SARS-CoV-2 confirmed infection through RT-PCR or who have already presented clinical and molecular diagnosis of COVID-19 prior to the study Individuals who have not underwent confirmatory tests for COVID-19 Breastfeeding Individuals with primary or acquired immunodeficiency Individuals affected by malignant neoplasms Patients treated with high-dose corticosteroids (equivalent to the prednisone dose of 20 mg/day or more) for more than two weeks Patients using other immunosuppressive therapies (antineoplastic chemotherapy, radiotherapy, among others) Individuals with autoimmune diseases Dermatological conditions at the vaccine site or generalized Individuals under treatment for active tuberculosis Individuals with a history of previous tuberculosis treatment Individuals with febrile symptoms [body temperature ≥ 37.5 celsius degree (ºC) in the last 48h] Participation in other prevention clinical trials for COVID-19 (vaccines already approved by ANVISA for use by the National Immunization Program are not included in this item) Report of vaccination with live microorganism administered in the month prior to randomization Require that, if another vaccination with live microorganism is required, it is administered in the month following randomisation (If the other live vaccine can be administered on the same day, this exclusion criterion does not apply) Known anaphylactic reaction to any ingredient in BCG vaccine Adverse reaction prior to BCG vaccine [significant local reaction (abscess) or suppurative lymphadenitis] BCG vaccine administered in the last year

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCG vaccine<br>0.1 ml of the reconstituted vaccine to be administered intradermally in the lower insertion of the deltoid muscle, preferably on the right side, in only one occasion | Biological: BCG vaccine<br>* Using aseptic methods, 1 mL of Sterile Water for Injection, is added to one vial of vaccine. Gently swirl the vial until a homogenous suspension is obtained. Avoid forceful agitation which may cause clumping of the mycobacteria. Drop the immunizing dose of 0.1 mL of BCG VACCINE from the syringe and needle onto the cleansed surface of the skin.<br>|
| Placebo Comparator: 0.9% sodium chloride (NaCl) saline solution<br>0.1 ml of 0.9% NaCl saline solution to be administered intradermally in the lower insertion of the deltoid muscle, preferably on the right side, in only one occasion | Biological: 0.9% sodium chloride (NaCl) saline solution<br>* A 0.1 ml of 0.9% NaCl saline solution applied intradermally in the lower insertion of the deltoid muscle of the right arm will be used as placebo, except contraindications or impossibilities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the cumulative incidence of SARS-CoV-2 infection | It is estimated that it will take 376 individuals in each of the comparison groups to ensure a statistical power of 85% for the detection of a risk difference of 5%, considering that the 6 months of follow-up, for a type I error of 5%. | 6 months | 
| Compare the cumulative incidence of severe forms of COVID-19 | With 376 individuals in each of the comparison groups the study will have a statistical power of approximately 75% for the detection of a risk difference of 2%, considering that the control group will have an accumulated incidence of more severe forms of COVID-19 of 2.5% after 6 months of follow-up, for a type I error of 5%. | 6 months | 
| Assess the BCG vaccine-mediated immune response in health care workers | SARS-CoV2 infection is estimated to occur in approximately 10% of BCG-vaccinated healthcare professionals (experimental group) and in 30% of non-BCG-vaccinated healthcare professionals (placebo group) In this scenario, with the bearing of 372 health professionals in each arm, SARS-CoV2 infection is expected to be detected in 50 BCG-vaccinated professionals and 150 professionals not vaccinated with BCG. For each subgroup (vaccinated and not vaccinated with BCG) it will be possible to identify the predictive biomarkers of infection by comparing infected professionals with those who were not infected with SARS-CoV2. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID 19, BCG vaccine