The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines

NCT05507671 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: BCG-COVID/484016302711489/2020
• Study Type: interventional
• Target: 556
• Locations: 1 country
• Sites: 4

Brief Summary

Clinical trial with randomized allocation in two arms (BCG vaccine versus placebo) of volunteers at risk but not yet infected nor vaccinated against SARS-CoV-2. Initially will be evaluated whether BCG has a protective role against severe form of the disease. After participants are vaccinated against COVID-19, it will be evaluated whether BCG favors the vaccine's efficacy. Volunteers will be recruited in three Brazilian states, with at least 250 seronegative in each group. The BCG-trained immunity stimulus will be investigated by assessing cytokines at D0 and D60 in a subsample of 50 participants per group. Until being vaccinated against COVID-19, the participants will be followed for up to 6 months, with visits scheduled every 2 months for interviews and immunoglobulin G (IgG) anti-SARS-CoV-2 antibodies. Those who become symptomatic at any time during the follow-up will be guided and monitored remotely daily until the end of their clinical evolution. After being vaccinated against COVID-19, visits to participants will be adjusted for the time of vaccination (VD), 20 days after the 1st dose (P1) and at least 30 days (P2) after the 2nd dose, with the aim of comparing the efficacy of the anti-SARS-CoV-2 vaccine in the two groups in the short and medium term. The study's conclusions on the efficacy of BCG in preventing severe COVID-19 will be based on: incidence of SARS-Cov-2 infection (defined as the emergence of IgG over the follow-up period); incidence of illness by COVID-19 (defined as the presence of symptoms among infected participants); intensity and duration of symptoms between cases of COVID-19 and frequency and duration of hospitalizations for COVID-19 in each group. The occurrence, type, frequency and intensity of adverse effects associated with vaccination of adults with BCG will be reported. The study's conclusions regarding the effect of BCG on efficacy of vaccines against COVID-19 will be based on: frequency of anti-SARS-CoV-2 neutralizing antibodies after the vaccine' 1st and 2nd doses in both groups.

Conditions

COVID-19

Keywords

COVID-19; SARS-CoV-2; BCG vaccine; Bacillus Calmette-Guérin; clinical trials; trained immunity

Outcome Measures

Primary Outcomes (4)

• Incidence of SARS-Cov-2 infection in both groups over the follow-up

  Appearance of IgG antibodies (seroconversion) in the participants not yet vaccinated against COVID-19

  Up to six months from recruitment day

• Incidence of illness by COVID-19 in both groups over the follow-up

  Presence of symptoms among subjects not vaccinated against COVID-19 diagnosed with infection after D0 or seroconverted

  Up to six months from recruitment day

• Intensity of the efficacy of the first dose of the vaccine against COVID-19

  Comparison of groups regarding frequency and titer (UI/ml) of anti-SARS-CoV-2 neutralizing antibodies after first dose of the specific vaccine, through the qualitative and semi-quatitative "SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT)" Genscript Kit

  Up to six months from recruitment day

• Duration of the efficacy of the second dose of the vaccine against COVID-19

  Comparison of groups regarding frequency and titer (UI/ml) of anti-SARS-CoV-2 neutralizing antibodies after second dose of the specific vaccine, through the qualitative and semi-quatitative "SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT)" Genscript Kit

  One year from recruitment day

Secondary Outcomes (3)

• Intensity of clinical presentation of SARS-CoV-2 infection in both groups over the follow-up

  One year from recruitment day

• Duration of symptoms among participants with COVID-19

  Six months from recruitment day

• Serum levels of cytokines after BCG vaccine stimulus (Trained Immunity effect)

  Two months from recruitment day

Other Outcomes (1)

• Adverse effects correlated with BCG vaccine in adults

  Six months from recruitment day

Study Arms (2)

BCG vaccine

ACTIVE COMPARATOR

BCG (Bacillus Calmette-Guérin) vaccine - 0,1ml intradermal

Biological: BCG (Bacillus Calmette-Guérin) vaccine

Placebo

PLACEBO COMPARATOR

Solvent of BCG vaccine - 0,1ml intradermal

Other: Placebo

Interventions

BCG (Bacillus Calmette-Guérin) vaccine BIOLOGICAL

Application of BCG vaccine (0.1 ml intradermal) in the right arm deltoid insertion

BCG vaccine

Placebo OTHER

Application of BCG solvent (0.1 ml intradermal) in the right arm deltoid insertion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Never been infected by SARS-Cov-2 - clinical history and absence of anti-SARS-CoV-2 IgM/IgG antibodies by the rapid test (immediate) and by serology test (later confirmation)
• Not having been vaccinated against COVID-19
• Be at least 18 years old

You may not qualify if:

• Have been vaccinated with BCG less than 6 months ago
• Have been vaccinated with BCG more than once in the past
• Present any classic contraindications for BCG - pregnancy, breastfeeding, acute febrile illness, severe allergy to one of the components, vaccination with other live vaccines in the last month (measles, yellow fever, herpes zoster), immunosuppression for any cause (congenital, illness, use of corticosteroids or immunosuppressants)
• Have had tuberculosis or contacted someone with tuberculosis
• Present signs of any current acute illness or have had a severe illness less than 15 days
• Present a skin lesion at the vaccine application site (right deltoid muscle)
• History of severe allergic reactions to any product: urticaria, glottis edema, angioedema, respiratory failure, bronchospasm
• History of serious autoimmune diseases: systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, hemolytic anemia, ankylosing spondylitis, pemphigus and others
• Immunocompromise for any reason (congenital, illness, use of corticosteroids or immunosuppressants)
• Presenting a risk comorbidity for severe COVID-19, such as: poorly controlled hypertension, decompensated heart disease (chronic, congenital or ischemic), pulmonary disease (chronic pneumopathy, poorly controlled asthma, chronic interstitial pneumopathy, others ...), disease advanced chronic kidney disease (use of dialysis), transplantation (of solid organs or bone marrow), uncontrolled diabetes

Sponsors & Collaborators

• Oswaldo Cruz Foundation: lead
• University of Sao Paulo: collaborator
• Federal University of Juiz de Fora: collaborator

Study Sites (4)

Policlínica Cardoso Fontes

Manaus, Amazonas, 69010-030, Brazil

Location

Universidade Federal de Juiz de Fora

Juiz de Fora, Minas Gerais, 36036-900, Brazil

Location

Centro Universitário do Pará

Belém, Pará, 66613-903, Brazil

Location

Oswaldo Cruz Foundation

Rio de Janeiro, Rio de Janeiro, 21040-360, Brazil

Location

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Related Links

• Coronavirus World Health Organization (WHO) data
• Coronavirus data
• Cases of coronavirus in Brazil
• Number of coronavirus cases in Brazil
• COVID in young people
• Respiratory syndrome
• Novel coronavirus in suspected human cases
• Novel Coronavirus (2019-nCoV) Reverse Transcription Polymerase Chain Reaction (RT-PCR) Diagnostic Panel
• COVID-19 epidemiological bulletin
• COVID-19: protecting health-care workers
• Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now
• BCG vaccination induces trained innate immunity in Bissau-Guinean adults over 50 years of age: a randomized trial
• Bacillus Calmette-guérin Vaccination to Prevent Infections of the Elderly
• Leprosy prevention and control measures
• Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study
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• BCG is a Good Immunotherapeutic Agent for Viral and Autoimmune Diseases: Is it a new weapon against coronavirus (COVID-19)?
• BCG Vaccination to Protect Healthcare Workers Against COVID-19
• Reducing Health Care Workers Absenteeism in COVID-19 Pandemic Through BCG Vaccine (BCG-CORONA)
• Vaccines available
• Normative Instruction Vaccination Calendar
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• Consolidated Headquarters of the Ministry of Health of Brazil
• Intradermal vaccination against tuberculosis
• Coronavirus Clinical Management Protocol (COVID-19) in Primary Health Care. Version 02, March 2020, Ministry of Health of Brazil
• Coronavirus
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• coronavirus Brazilian boletim

MeSH Terms

Conditions

COVID-19

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Simone Ladeia-Andrade, MD PhD

  Oswaldo Cruz Institute, Oswaldo Cruz Foundation

  PRINCIPAL INVESTIGATOR

• Igor C Johansen, PhD

  University of Campinas, Brazil

  STUDY CHAIR

• Marcelo U Ferreira, MD PhD

  University of Sao Paulo

  STUDY CHAIR

• Kezia KG Scopel, PhD

  Universidade Federal de Juiz de Fora

  STUDY CHAIR

• Helena LC Santos, PhD

  Oswaldo Cruz Institute, Oswaldo Cruz Foundation

  STUDY CHAIR

• Haroldo J Matos, MD PhD

  Centro Universitário do Pará

  STUDY CHAIR

• Irineide A Antunes, MD

  Policlínica Cardoso Fontes de Manaus

  STUDY CHAIR

• Lucilaide O Santos, MD

  Fundação de Medicina Tropical Doutor Heitor Vieira Dourado

  STUDY CHAIR

• Sandra HC Tibiriça, MD PhD

  Universidade Federal de Juiz de Fora

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will not be informed if they received BCG or placebo. They will be informed that the injection may or may not give a local reaction regardless of what they receive. Blood samples for serological and cytokine studies will be coded and the laboratory technician will not know which samples are from participants who received BCG or placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-arm study, BCG vaccine versus placebo, to assess the effect of BCG in preventing severe form of covid19 and improving the efficacy of anti-SARS-CoV-2 vaccines

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: August 19, 2022
• Study Start: May 27, 2021
• Primary Completion: July 31, 2023
• Study Completion: December 31, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (4)