Using BCG Vaccine to Enhance Non-specific Protection of Health Care Workers During the COVID-19 Pandemic. A Randomized Controlled Multi-center Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,293
- 试验地点
- 2
- 主要终点
- Number of days of unplanned absenteeism for any reason
研究概览
简要总结
Background: The COVID-19 pandemic challenges the available hospital capacity, and this will be augmented by absenteeism of healthcare workers (HCW). HCW are at high risk, currently HCW constitute 20% of all the COVID-19 cases in Denmark. Strategies to prevent absenteeism of HCW are urgently needed.
Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other infections; significant reductions in morbidity and mortality have been reported, and a plausible immunological mechanism has been identified.
We hypothesize that BCG vaccination can reduce HCW absenteeism during the COVID-19 pandemic.
Primary objective: To reduce absenteeism among HCW with direct patient contacts during the COVID-19 epidemic. Secondary objective: To reduce the number of HCW that are infected with SARS-CoV-2 during the COVID-19 epidemic and to reduce the number of hospital admissions amongst HCW with direct patient contacts during the COVID-19 epidemic.
Study design: A multi-center randomized placebo controlled trial. Study population: 1500 HCW with direct patient contacts; defined as nurses, physicians and other medical staff working at emergency rooms and wards where COVID-infected patients are treated.
Intervention: Participants will be randomized 1:1 to intradermal administration of a standard dose of BCG vaccine or placebo (saline).
Main study parameters/endpoints: Primary endpoint: Number of days of (unplanned) absenteeism for any reason. Secondary endpoints: Number of days of (unplanned) absenteeism because of documented COVID infection. Cumulative incidence of hospital admissions.
Risk for participants and impact: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the potential beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of COVID infection.
详细描述
BACKGROUND Health-care workers face an elevated risk of exposure to - and infection with - SARS-CoV-2. It is imperative to ensure the safety, health and fitness of hospital personnel in order to safeguard continuous patient care. Strategies to prevent COVID-19 or to mitigate its clinical consequences are urgently needed.
Bacillus Calmette-Guérin (BCG) was developed as a vaccine against tuberculosis, but our group has shown that it can protect against death from other infections, it has what we have called non-specific effects (NSEs).[3] In clinical studies, BCG vaccination was associated with less child mortality, mainly as a result of reduced neonatal sepsis and respiratory infections. In a WHO-commissioned meta-analysis, BCG was associated with 42% (95%CI: 24-55%) lower child mortality.
NSEs of BCG are not limited to children. An Indonesian trial has shown that consecutive BCG vaccination for 3 months reduced the incidence of acute upper tract respiratory infections by 80% (95%CI=22-95%).
It has been recently demonstrated that the non-specific beneficial effects of BCG vaccination are due to epigenetic and metabolic reprogramming of innate immune cells, a process termed 'trained immunity'. E.g. among humans receiving yellow fever vaccine virus, those who had received BCG had - compared to placebo treated subjects - lower viral load, and improved anti-viral responses.
We hypothesize that BCG vaccination may induce (partial) protection against susceptibility to and/or severity of COVID-19. This study will evaluate the efficacy of BCG to improve the clinical course of COVID-19 and to prevent absenteeism.
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 be blinded to treatment. The physicians administering the BCG vaccine or placebo will not be blinded. In case of serious adverse events, the participant can be unblinded after consultation with the coordinating PI or sponsor.
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In order to be eligible to participate in this study, a subject must meet the following criteria:
- •Adult (≥18 years);
- •Hospital personnel caring for patients with COVID-19.
排除标准
- •Known allergy to (components of) the BCG vaccine or serious adverse events to prior BCG administration
- •Known active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species
- •Previous M. tuberculosis infection
- •Previous confirmed COVID-19 infection
- •Fever (>38 C) within the past 24 hours
- •Suspicion of active viral or bacterial infection
- •Pregnancy
- •Severely immunocompromised subjects (This exclusion category comprises a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) subjects with solid organ transplantation; c) subjects with bone marrow transplantation; d) subjects under chemotherapy; e) subjects with primary immunodeficiency; f) treatment with any anti-cytokine therapies. g) treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months)
- •Active solid or non-solid malignancy or lymphoma within the prior two years;
- •Direct involvement in the design or the execution of the BCG-DENMARK-COVID study
- •Employed to the hospital < 22 hours per week
- •Not in possession of a smartphone/tablet.
结局指标
主要结局
Number of days of unplanned absenteeism for any reason
时间窗: 6 months
次要结局
- Number of days of (unplanned) absenteeism due to infections(6 months)
- The number of days of self-reported fever (≥38 °C)(6 months)
- The cumulative incidence of documented COVID(6 months)
- Number of days of (unplanned) absenteeism due to respiratory infections(6 months)
- The cumulative incidence of Intensive Care Admission for any reason(6 months)
- The number of days of self-reported acute respiratory symptoms(6 months)
- Cumulative incidence of infectious disease episodes, in particular respiratory infections(6 months)
- The cumulative incidence of self-reported acute respiratory symptoms(6 months)
- Cumulative incidence of all-cause and infectious hospital admissions, in particular respiratory infections(6 months)
- The number of days of absenteeism, because of imposed quarantine as a result of exposure to SARS-CoV-2(6 months)
- The number of days of unplanned absenteeism because of self-reported acute respiratory symptoms(6 months)
- The cumulative incidence of death for any reason(6 months)
- The cumulative incidence of death due to documented COVID(6 months)
- The number of days of unplanned absenteeism, because of documented COVID(6 months)
- The number of days of absenteeism, because of imposed quarantine as a result of having acute respiratory symptoms, fever or documented SARS- CoV-2 infection(6 months)
- The cumulative incidence of Intensive Care Admission due to documented COVID(6 months)
- The cumulative incidence of Hospital Admission due to documented COVID(6 months)