Bacillus Calmette-Guerin Vaccination as Defense Against SARS-CoV-2: A Randomized Controlled Trial to Protect Health Care Workers by Enhanced Trained Immune Responses
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 659
- 试验地点
- 6
- 主要终点
- Number of New COVID 19 Infections
研究概览
简要总结
SARS-CoV-2 spreads rapidly throughout the world. A large epidemic would seriously challenge the available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Strategies to prevent infection and disease severity of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported morbidity and mortality reductions as high as 70%. Furthermore, in our preliminary analysis, areas with existing BCG vaccination programs appear to have lower incidence and mortality from COVID191. The investigators hypothesize that BCG vaccination can reduce HCW infection and disease severity during the epidemic phase of SARS-CoV-2.
详细描述
Study design: A placebo-controlled adaptive multi-center randomized controlled trial.
Study population: High risk HCW with direct patient contacts, defined as physician assistants, respiratory therapists, nurses, physicians or other HCWs working at emergency rooms, ICUs and in locations within hospitals where COVID-infected patients are treated.
Intervention: Participants will be randomized between intradermal administration of BCG vaccine or placebo in a 1:1 ratio.
Recruitment, Randomization, treatment allocation, and blinding
A standardized, IRB approved email will be sent to department chairs describing the study. A research coordinator will reach out to interested participants via phone with the help of an IRB-approved verbal script to introduce the study, confirm eligibility and provide further instructions on how to access and sign the IRB-approved ICD via REDCap using their own electronic devices. It is important that the investigators obtain the consent via REDCAp to a) avoid direct person-to-person contact and comply with social distancing imposed recommendations, and b) minimize the waste of reconstituted BCG by allowing the research personnel to schedule vaccinations in a controlled fashion. Patient registration into the trial will happen immediately after consent has been provided and will involve entering of baseline information into an electronic data capture system (RedCap).
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, Investigator)
盲法说明
Randomization will be done centrally and computer generated with stratification per hospital in random blocks of 2, 4 and 6. The BCG vaccine will be administered by research nurses. Participants and investigators will be blinded. The research nurse that administers the BCG vaccine or placebo will not be blinded. This research nurse will not be involved in the collection of outcome data.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult (≥18 years)
- •Male or female
- •Hospital personnel taking care for patients with known or suspected SARS-CoV-2 infection and providing, on average, at least 25 hours per week of direct patient care
排除标准
- •Known allergy to (components of) the BCG vaccine or serious adverse events to prior BCG administration
- •Known active or latent Mycobacterium tuberculosis or with another mycobacterial species. A history with- or a suspicion of M. tuberculosis infection.
- •Fever (>38 C) within the past 24 hours
- •Age > 75 years
- •Pregnancy or planning pregnancy within 30 days of study enrollment
- •Breastfeeding
- •Suspicion of active viral or bacterial infection
- •Any Immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) subjects with known neutropenic with less than 1500 neutrophils/mm3; c) subjects with solid organ transplantation; d) subjects with bone marrow transplantation; e) subjects under chemotherapy; f) subjects with primary immunodeficiency; g) known severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine therapies. i) treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months
- •Living with someone who is immunosuppressed or taking immunosuppressive drugs
- •Previous documented infection with COVID19
- •Active solid or non-solid malignancy or lymphoma within the prior two years
- •Direct involvement in the design or the execution of the study
- •Expected absence from work of ≥4 of the following 12 weeks due to any reason (holidays, maternity leave, retirement, planned surgery etc)
- •Not in possession of a smartphone
- •Inability to keep the vaccine site covered in the case of a draining pustule.
研究组 & 干预措施
BCG Group
FDA-approved BCG Tice strain, procured from Merck, will be used. The vaccine will be reconstituted according to the package insert. In brief, a vial containing ~1x10^8 CFU of lyophilized BCG will be reconstituted in 50 mL of saline. A single dose will consist of 0.1 mL (~2x10^5 CFU) will be administered by slow intradermal injection using a 25 gauge/ 0.5 mm syringe in the deltoid area.
干预措施: BCG Vaccine (Biological)
Placebo Group
A single dose will consist of 0.1 mL saline
干预措施: Placebo Vaccine (Biological)
结局指标
主要结局
Number of New COVID 19 Infections
时间窗: 6 months
The primary outcome measure is development of COVID19 infection. This will be reported as the number of individuals receiving the intervention who are PCR-positive or seroconvert, defined as number of new cases during the 6 month time period
次要结局
- Disease Severity(6 months)