Randomized Controlled Trial Evaluating the Efficacy of Vaccination With Bacillus Calmette and Guérin (BCG) in the Prevention of COVID-19 Via the Strengthening of Innate Immunity in Health Care Workers
试验速览
- 阶段
- 3 期
- 入组人数
- 1,120
- 试验地点
- 2
- 主要终点
- Incidence of documented COVID-19 among health care workers exposed to SARS CoV2 and vaccinated with BCG compared to placebo.
研究概览
简要总结
Healthcare Workers (HCW) are at high risk for COVID-19. In addition to the risk of serious forms among HCW, significant absenteeism due to illness would have dramatic consequences in our ability to fight COVID-19. No coronavirus vaccine is available today and drug treatments are only at the start of clinical evaluation. Available since 1921, the bacillus Calmette and Guérin (BCG) is the most widely used vaccine in the world (> 3 billion doses administered) with an extremely low rate of adverse effects. BCG is indicated for the prevention of tuberculosis (TB), but more recent studies have shown that it also has nonspecific immune properties which may be interesting in the current COVID-19 epidemic. Data in mice and in humans have demonstrated protection conferred by BCG against viral respiratory infections such as influenza. In countries with high endemic TB, BCG decreases the incidence of acute respiratory infections by up to 80%, neonatal BCG vaccination has been shown to greatly reduce the risk of sepsis and of hospitalization of children for reasons other than TB. A recent study conducted in South Africa showed that re-vaccination with BCG in adults reduced the incidence of respiratory infections by 70% compared to unvaccinated controls. Beyond respiratory infections, BCG has also shown protective effects against inflammatory diseases. These non-specific beneficial effects are likely linked to the induction of "trained innate immunity", implying epigenetic and metabolic re-programming of innate immune cells. It is therefore possible that revaccination with BCG could significantly reduce the incidence and severity of COVID-19. Very recent ecological observations indeed suggest an inverse correlation between BCG vaccination coverage and the morbidity and mortality of COVID-19. In this context several trials began in Europe and Australia to evaluate the efficacy of BCG vaccination in populations at risk of exposure (HCW) or severe disease (elderly). This study is aligned with studies carried out in Australia, The Netherlands and Spain. In contrast to these latter studies, virtually all French study participants have been vaccinated in their childhood, since BCG vaccination was mandatory in France in neonates until 2007, and in HCW until recently. Therefore, the French study will be in a unique situation to evaluate the effect of re-vaccination with BCG in the context of BCG priming decades before revaccination.
详细描述
Randomized, multicenter phase III controlled trial, in 2 parallel arms:
- One group vaccinated with BCG
- One group receiving placebo (0.9 % saline) Randomization in a 1: 1 ratio will be stratified on the center. The study will be proposed to all heath care workers eligible. At screening, the investigator will propose the study to the participant and explain the details by providing an information letter. After signature of the consent, evaluations specific for the study will be undertaken, such as clinical examination, blood sampling, nasopharyngeal sampling in case of clinical signs.
At the inclusion visit, participants corresponding to the inclusion criteria will be randomized to receive BCG or placebo.
Participants will receive a single dose of BCG vaccine (or placebo). The adult dose of BCG vaccine (or placebo) is 0.1 mL injected intradermally over the distal insertion of the deltoid muscle onto the humerus (approximately one third down the upper arm).
Follow-up visits will be done respectively at M3 and M6 and phone contacts between these two visits.
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
- Single (Participant)
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
- •Individual (Male and female) aged 18 or over.
- •Healthcare Worker (medical or non-medical) from hospitals in direct contact with COVID-19 patients.
- •Participants must give their written consent before any trial procedure.
- •Participants covered by social security regimen (excepting AME).
- •Healthy according to the opinion of the investigator.
排除标准
- •Has any BCG vaccine contraindication, known allergy to the BCG vaccine or SAE to prior BCG vaccination.
- •History of tuberculosis
- •People with acquired or innate immunodeficiency.
- •People have already been infected with SARS Cov-2 (virological documentation or TDM or seropositive if serology available).
- •People who could not commit to follow-up for 6 months.
- •People not in good general condition, as assessed by the investigator.
- •People included in other clinical trials assessing treatment.
- •Pregnant or breastfeeding or positive urine pregnancy at enrolment visit.
- •BCG vaccine given within the last year.
- •Another live vaccine administered in the month prior to randomization.
- •History of anaphylaxis following vaccination.
- •Receiving medical treatment that affects the immune response or other immunosuppressive therapy in the last year. These therapies include systemic corticosteroids (more than or equal to 10 mg for more than or equal to 2 weeks), immunosuppressant, biological agents (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha).
- •Another vaccine administered in the month prior to inclusion and randomization.
- •Fever > 38°C within the past 24 hours
- •People with malignancies (e.g. lymphoma, leukemia, Hodgkin's disease or other tumors of the reticuloendothelial system) or infected with HIV
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Acute severe febrile illness
- •Generalized infected skin conditions
- •People under legal protection measure (tutorship, curatorship or safeguard measures)
结局指标
主要结局
Incidence of documented COVID-19 among health care workers exposed to SARS CoV2 and vaccinated with BCG compared to placebo.
时间窗: during the study period of 6 months
Documented COVID-19, i.e. symptomatic COVID-19 confirmed by either * positive nasopharyngeal tests for SARS CoV2 * and/or by thoracic tomodensitometry compatible with the diagnosis. * and/or SARS CoV2 seroconversion
次要结局
- Incidence of subjects with any respiratory infection among BCG-vaccinated health care workers compared to placebo.(during the study period of 6 months.)
- Numbers of sick days and numbers of sick leaves among BCG-vaccinated health care workers compared to placebo.(during the study period of 6 months)
- Numbers of subjects with BCG-related advers events among BCG-vaccinated health care workers compared to placebo.(30 days after BCG revaccination)
- Numbers of COVID-19 patients requiring hospitalization in ICU and O2, artificial ventilation or extracorporal membrane oxygenation, or deaths in BCG-vaccinated health care workers compared to placebo(during the study period of 6 months.)
- Incidence of asymptomatic SARS CoV2 seropositive subjects among BCG-vaccinated health care workers compared to placebo.(during the study period of 6 months.)
- Numbers and intensity of changes in innate immune markers after SARS CoV2 infection among BCG-vaccinated health care workers compared to placebo.(during the study period of 6 months.)