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

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ClinicalTrials.gov Identifier: NCT05507671
Recruitment Status : Recruiting
First Posted : August 19, 2022
Last Update Posted : August 19, 2022
Sponsor:
Collaborators:
University of Sao Paulo
Federal University of Juiz de Fora
Information provided by (Responsible Party):
Oswaldo Cruz Foundation

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.


Condition or disease Intervention/treatment Phase
COVID-19 Biological: BCG (Bacillus Calmette-Guérin) vaccine Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 556 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: Double (Participant, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Prevention
Official Title: The Role of the Bacillus Calmette-Guérin Vaccine (BCG) in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) Vaccines
Actual Study Start Date : May 27, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Active Comparator: BCG vaccine
BCG (Bacillus Calmette-Guérin) vaccine - 0,1ml intradermal
Biological: BCG (Bacillus Calmette-Guérin) vaccine
Application of BCG vaccine (0.1 ml intradermal) in the right arm deltoid insertion

Placebo Comparator: Placebo
Solvent of BCG vaccine - 0,1ml intradermal
Other: Placebo
Application of BCG solvent (0.1 ml intradermal) in the right arm deltoid insertion




Primary Outcome Measures :
  1. Incidence of SARS-Cov-2 infection in both groups over the follow-up [ Time Frame: Up to six months from recruitment day ]
    Appearance of IgG antibodies (seroconversion) in the participants not yet vaccinated against COVID-19

  2. Incidence of illness by COVID-19 in both groups over the follow-up [ Time Frame: Up to six months from recruitment day ]
    Presence of symptoms among subjects not vaccinated against COVID-19 diagnosed with infection after D0 or seroconverted

  3. Intensity of the efficacy of the first dose of the vaccine against COVID-19 [ Time Frame: Up to six months from recruitment day ]
    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

  4. Duration of the efficacy of the second dose of the vaccine against COVID-19 [ Time Frame: One year from recruitment day ]
    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


Secondary Outcome Measures :
  1. Intensity of clinical presentation of SARS-CoV-2 infection in both groups over the follow-up [ Time Frame: One year from recruitment day ]
    Comparison of groups regarding the frequency of infected with mild, moderate, serious or critical symptoms (according to detailed description in item 2.9-Clinical Evolution) and deaths by COVID-19 during the follow-up. The information will be obtained through daily telephone interview, self-completion of a questionnaire and hospitalization data.

  2. Duration of symptoms among participants with COVID-19 [ Time Frame: Six months from recruitment day ]
    Comparison of groups regarding the duration (number of days) of symptoms among participants who acquire COVID-19. The information will be obtained through daily telephone interview, self-completion of a questionnaire and hospitalization data

  3. Serum levels of cytokines after BCG vaccine stimulus (Trained Immunity effect) [ Time Frame: Two months from recruitment day ]
    Comparison of serum concentrations (pg/mL) of cytokines TNF-α, IFN-γ, IL-1β, IL-4, IL-6 and IL-10 at D0 versus D60 of 50 participants of BCG group compared to 50 participants of placebo group


Other Outcome Measures:
  1. Adverse effects correlated with BCG vaccine in adults [ Time Frame: Six months from recruitment day ]
    Occurrence, type, frequency and intensity of adverse effects correlated with BCG revaccination obtained from obtained by interviewing those vaccinated with BCG (descriptive data)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA:

  • 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

EXCLUSION CRITERIA:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05507671


Contacts
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Contact: Simone Ladeia-Andrade, MD PhD 2125621302 ext +55 sladeia@ioc.fiocruz.br
Contact: Marcelo U Ferreira, MD PhD 1130917746 ext +55 muferrei@usp.br

Locations
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Brazil
Policlínica Cardoso Fontes Recruiting
Manaus, Amazonas, Brazil, 69010-030
Contact: Irineide A Antunes, MD    +55(92)3627-8204    irineide_antunes@yahoo.com.br   
Contact: Lucilaide O Santos, MD    +55(92)994371916    santos.lucilaide@gmail.com   
Universidade Federal de Juiz de Fora Recruiting
Juiz de Fora, Minas Gerais, Brazil, 36036-900
Contact: Kezia KG Scopel, PhD    +55(32)21023219    keziagscopel@gmail.com   
Contact: Sandra HC Tibiriça, MD PhD    +55(32)988537708    shctibi@gmail.com   
Centro Universitário do Pará Recruiting
Belém, Pará, Brazil, 66613-903
Contact: Haroldo J Matos, MD PhD    +55(91)993251672    haroldodematos@gmail.com   
Oswaldo Cruz Foundation Not yet recruiting
Rio de Janeiro, Brazil, 21040-360
Contact: Simone L Andrade, MD-PhD    +55-21-25621302    sladeia@ioc.fiocruz.br   
Contact: Marcelo U Ferreira, MD-PhD    +55-11-30917746    muferrei@usp.br   
Sub-Investigator: Simone L Andrade, PhD         
Sponsors and Collaborators
Oswaldo Cruz Foundation
University of Sao Paulo
Federal University of Juiz de Fora
Investigators
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Principal Investigator: Simone Ladeia-Andrade, MD PhD Oswaldo Cruz Institute, Oswaldo Cruz Foundation
Study Chair: 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
Additional Information:

Publications:

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Responsible Party: Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier: NCT05507671    
Other Study ID Numbers: BCG-COVID/484016302711489/2020
First Posted: August 19, 2022    Key Record Dates
Last Update Posted: August 19, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Oswaldo Cruz Foundation:
COVID-19
SARS-CoV-2
BCG vaccine
Bacillus Calmette-Guérin
clinical trials
trained immunity
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs