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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 556
- 试验地点
- 4
- 主要终点
- Duration of the efficacy of the second dose of the vaccine against COVID-19
研究概览
简要总结
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.
详细描述
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OBJECTIVE- To evaluate the role of the BCG vaccine against the severe form of COVID-19 and in improving the efficacy of anti-SARS-CoV-2 vaccines through a two-arm clinical trial comparing BCG versus placebo. Specifically:
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Assess whether BCG vaccine is able to stimulate the nonspecific immune response (trained immunity)
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Verify whether BCG is able to protect against SARS-CoV-2 infection
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Assess whether BCG is able to protect infected with SARS-CoV-2 against illness
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Assess whether BCG is able to protect subjects with COVID-19 against its severe form
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Evaluate whether BCG can favor the effectiveness of doses of anti-SARS-CoV-2 vaccines
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Knowing whether revaccination of adults with BCG causes unexpected adverse reactions
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METHODOLOGY:
2.1 STUDY MODEL: Two-arm Clinical Trial - intervention (BCG) versus placebo
2.2 STUDY POPULATION: Volunteers not yet infected with SARS-CoV-2 or vaccinated against COVID-19, who can be essential service workers with frequent contact with the population: workers in health posts, users of the public health network due to others non-serious illnesses, police officers, employees of pharmacies, supermarkets, stores and others
Sampling: As the real prevalence of SARS-CoV-2 infection in the eligible population of the different recruitment sites is unknown, a prevalence of 50% was considered (it provides the largest sample size) and estimated that the post-BCG prevalence would decrease at least 10% if its effectiveness to be demonstrated. Thus, it was found a sample of 385 subjects. Considering losses, a minimum of 400 participants will be recruited, with at least 200 in each group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BCG vaccine
BCG (Bacillus Calmette-Guérin) vaccine - 0,1ml intradermal
干预措施: BCG (Bacillus Calmette-Guérin) vaccine (Biological)
Placebo
Solvent of BCG vaccine - 0,1ml intradermal
干预措施: Placebo (Other)
结局指标
主要结局
Duration of the efficacy of the second dose of the vaccine against COVID-19
时间窗: 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
Incidence of SARS-Cov-2 infection in both groups over the follow-up
时间窗: Up to six months from recruitment day
Appearance of IgG antibodies (seroconversion) in the participants not yet vaccinated against COVID-19
Incidence of illness by COVID-19 in both groups over the follow-up
时间窗: Up to six months from recruitment day
Presence of symptoms among subjects not vaccinated against COVID-19 diagnosed with infection after D0 or seroconverted
Intensity of the efficacy of the first dose of the vaccine against COVID-19
时间窗: 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
次要结局
- Intensity of clinical presentation of SARS-CoV-2 infection in both groups over the follow-up(One year from recruitment day)
- Serum levels of cytokines after BCG vaccine stimulus (Trained Immunity effect)(Two months from recruitment day)
- Duration of symptoms among participants with COVID-19(Six months from recruitment day)