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

Primary Purpose

COVID 19 Vaccine

Status

Active

Phase

Phase 2

Locations

Brazil

Study Type

Interventional

Intervention

BCG vaccine

0.9% sodium chloride (NaCl) saline solution

About this trial

This is an interventional prevention trial for COVID 19 Vaccine focused on measuring COVID 19, BCG vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Universidade Federal do Rio de Janeiro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BCG vaccine

0.9% sodium chloride (NaCl) saline solution

Arm Description

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

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

Outcomes

Primary Outcome Measures

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%.

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%.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04659941

First Posted

December 8, 2020

Last Updated

May 10, 2023

Sponsor

Universidade Federal do Rio de Janeiro

Collaborators

Ministry of Science and Technology, Brazil

1. Study Identification

Unique Protocol Identification Number

NCT04659941

Brief Title

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

Acronym

ProBCG

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 1, 2020 (Actual)

Primary Completion Date

October 1, 2022 (Actual)

Study Completion Date

April 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Universidade Federal do Rio de Janeiro

Collaborators

Ministry of Science and Technology, Brazil

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief Summary

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

Study detailed description can be seen on the protocol attached.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID 19 Vaccine

Keywords

COVID 19, BCG vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

752 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

BCG vaccine

Arm Type

Experimental

Arm Description

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

Arm Title

0.9% sodium chloride (NaCl) saline solution

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

BCG vaccine

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

0.9% sodium chloride (NaCl) saline solution

Intervention Description

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.

Primary Outcome Measure Information:

Title

Compare the cumulative incidence of SARS-CoV-2 infection

Description

Time Frame

6 months

Title

Compare the cumulative incidence of severe forms of COVID-19

Description

Time Frame

6 months

Title

Assess the BCG vaccine-mediated immune response in health care workers

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fernanda Carvalho de Q Mello, PHD

Organizational Affiliation

Universidade Federal do Rio de Janeiro

Official's Role

Principal Investigator

Facility Information:

Facility Name

Universidade Federal do Rio de Janeiro

City

Rio De Janeiro

State/Province

ZIP/Postal Code

21941-590

Country

Brazil

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

21673035

Citation

Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, Stensballe L, Diness BR, Lausch KR, Lund N, Biering-Sorensen S, Whittle H, Benn CS. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis. 2011 Jul 15;204(2):245-52. doi: 10.1093/infdis/jir240.

Results Reference

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PubMed Identifier

27157064

Citation

Goodridge HS, Ahmed SS, Curtis N, Kollmann TR, Levy O, Netea MG, Pollard AJ, van Crevel R, Wilson CB. Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol. 2016 Jun;16(6):392-400. doi: 10.1038/nri.2016.43. Epub 2016 May 9.

Results Reference

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PubMed Identifier

24192057

Citation

Kleinnijenhuis J, Quintin J, Preijers F, Benn CS, Joosten LA, Jacobs C, van Loenhout J, Xavier RJ, Aaby P, van der Meer JW, van Crevel R, Netea MG. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun. 2014;6(2):152-8. doi: 10.1159/000355628. Epub 2013 Oct 30.

Results Reference

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PubMed Identifier

27102489

Citation

Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ. Trained immunity: A program of innate immune memory in health and disease. Science. 2016 Apr 22;352(6284):aaf1098. doi: 10.1126/science.aaf1098. Epub 2016 Apr 21.

Results Reference

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PubMed Identifier

24845462

Citation

Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res. 2014 Aug;59(1-3):118-28. doi: 10.1007/s12026-014-8534-z.

Results Reference

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PubMed Identifier

32437659

Citation

Netea MG, Giamarellos-Bourboulis EJ, Dominguez-Andres J, Curtis N, van Crevel R, van de Veerdonk FL, Bonten M. Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection. Cell. 2020 May 28;181(5):969-977. doi: 10.1016/j.cell.2020.04.042. Epub 2020 May 4.

Results Reference

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PubMed Identifier

32330314

Citation

Ozdemir C, Kucuksezer UC, Tamay ZU. Is BCG vaccination affecting the spread and severity of COVID-19? Allergy. 2020 Jul;75(7):1824-1827. doi: 10.1111/all.14344. Epub 2020 May 12. No abstract available.

Results Reference

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PubMed Identifier

32756371

Citation

Urashima M, Otani K, Hasegawa Y, Akutsu T. BCG Vaccination and Mortality of COVID-19 across 173 Countries: An Ecological Study. Int J Environ Res Public Health. 2020 Aug 3;17(15):5589. doi: 10.3390/ijerph17155589.

Results Reference

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

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