Global and Immigrant Health, Baylor College of Medicine, Houston, TX, 77030, USA.
Radboud Center for Infectious Diseases, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Trials. 2023 Oct 4;24(1):636. doi: 10.1186/s13063-023-07662-w.
A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.
This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models.
It is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic.
ClinicalTrials.gov NCT04348370. Registered on April 16, 2020.
大规模疫情，如 SARS-CoV-2 引起的疫情，严重挑战了现有医院的容量，如果医护人员（HCW）也感染，情况将更加严重。卡介苗是一种预防结核病的疫苗，具有体外和体内针对其他呼吸道感染的保护非特异性作用。初步分析表明，世界上存在卡介苗接种计划的地区 COVID-19 的发病率和死亡率较低。我们假设卡介苗接种可以降低 SARS-CoV-2 感染和疾病严重程度。
这将是一项安慰剂对照的适应性多中心随机对照试验。共有 1800 名被认为处于高风险的个体，包括患有合并症（高血压、糖尿病、肥胖、气道反应性疾病、吸烟者）、少数民族、老年人、教师、警察、餐馆服务员、送货人员、被定义为在医疗机构、医院、医疗中心或诊所（兽医、牙科、眼科）工作的医护人员以及急救人员（护理人员、消防员或执法人员），将被随机分为两组。治疗组将接受皮内卡介苗疫苗或安慰剂（生理盐水）注射，比例为 1:1。将对个体进行跟踪，以发现 SARS-CoV-2 感染和严重程度的证据，并采集全血以跟踪免疫标志物，一个子研究将包括认知功能和脑成像。大多数个体将随访 6 个月，可选择再延长 6 个月，认知子研究的持续时间为 2 年。我们将绘制 Kaplan-Meier 曲线，比较组间曲线，并使用 Cox 比例风险模型报告风险比和 p 值。
预计该试验将允许通过减轻 SARS-CoV-2 感染的临床病程，在高危医护人员的人群中评估卡介苗接种的效果，并为当前疫情期间的决策提供信息。
ClinicalTrials.gov NCT04348370。于 2020 年 4 月 16 日注册。
