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

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

Interventions

BIOLOGICAL

BCG (Bacillus Calmette-Guérin) vaccine

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

OTHER

Placebo

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

Sponsors & Collaborators

• University of Sao Paulo

  collaborator OTHER

• Federal University of Juiz de Fora

  collaborator OTHER

• Oswaldo Cruz Foundation

  lead OTHER

Principal Investigators

• Simone Ladeia-Andrade, MD PhD · Oswaldo Cruz Institute, Oswaldo Cruz Foundation

• Igor C Johansen, PhD · University of Campinas, Brazil

• Marcelo U Ferreira, MD PhD · University of Sao Paulo

• Kezia KG Scopel, PhD · Universidade Federal de Juiz de Fora

• Helena LC Santos, PhD · Oswaldo Cruz Institute, Oswaldo Cruz Foundation

• Haroldo J Matos, MD PhD · Centro Universitário do Pará

• Irineide A Antunes, MD · Policlínica Cardoso Fontes de Manaus

• Lucilaide O Santos, MD · Fundação de Medicina Tropical Doutor Heitor Vieira Dourado

• Sandra HC Tibiriça, MD PhD · Universidade Federal de Juiz de Fora

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-05-27

Primary Completion

2023-07-31

Completion

2025-12-31

Countries

• Brazil

Study Locations