A Multi-centre, Randomised, Double-blind, Placebo-controlled Phase III Clinical Trial Evaluating the Effect of BCG Vaccination on the Incidence and Severity of SARS-CoV-2 Infections Among Healthcare Professionals During the COVID-19 Pandemic in Poland
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 1,000
- 试验地点
- 6
- 主要终点
- death and life- or health-threatening condition (cardiac arrest with effective resuscitation, shock, severe respiratory failure, severe renal failure, stroke/transient cerebral ischaemia)
研究概览
简要总结
Countries that have not carried out universal mass vaccination against tuberculosis (BCG) have been shown to have higher incidence and death rates due to COVID-19 than countries with mass, long-term BCG immunization programmes.
The aim of the study is to answer the following questions:
- Does BCG vaccination affect the course of COVID-19 (number of cases/deaths/severity of symptoms)?
- Will the course of COVID-19 be milder among subjects with a negative TB skin test (PPD RT 23 SSI) after an additional dose of BCG than in case of non-vaccinated subjects?
- Do people with a positive TB skin test have a milder course of COVID-19 infection than people with a negative test result?
A multicenter, randomized, partially blinded, placebo-controlled study will be conducted in Rzeszow/Krakow/ Katowice/Warsaw on a group of 1000 volunteers, health care workers according to the following schedule: V 0-1: inclusion/informed consent/interview; V2: administration of TB skin test/anti-SARS-CoV-2 IgG test/serum banking*; V3: TB skin test (TST) interpretation and subjects' division into three groups: (I) positive TST - observation; (II) negative TST- BCG-10 vaccination; (III) negative TST - placebo. Division into groups II and III based on randomisation; V4: serum banking*. Parallel beginning from V3, weekly telephone monitoring participants' health status; In case of COVID-19 symptoms a nasopharyngeal swab to confirm SARS-CoV-2 infection + serum banking*. V5: 3 months after vaccination at the end of the study: history/anti-SARS-CoV-2 IgG test, serum banking*.
Statistical analysis - comparison of the course of COVID-19 in groups: (I) with positive TST + observation, (II) with negative TST + BCG, (III) with negative TST + placebo - should demonstrate whether mass BCG vaccination has an impact on the incidence and course of COVID-19.
* to measure the level of cytokines involved in cell-mediated immunity process
详细描述
Trial design:
The multicentre, randomised, double-blind placebo-controlled trial will be conducted in five centres: Rzeszów, Kraków, Katowice, Warsaw (2 centres) in a group of 1000 volunteers, health care workers (physicians, nurses, midwives, paramedics, laboratory diagnosticians, electroradiology technicians, physiotherapists, nutritionists, and orderlies), both women and men aged ≥25 years and employed in health care facilities in the above-mentioned cities and provinces.
Planned duration of the trial:
2-4 weeks -recruitment, inclusion in the trial, RT 23 testing, BCG-10 vaccination 3 months - observation after vaccination 18 months, calculated from the date of trial initiation (visit no. "0"); during this period the subjects are to provide the Research Team with telephone information about possible hospitalisations and other unexpected, sudden or significant changes in health.
Recruitment period:
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Due to trial blindness, the team (a doctor and nurse) participating in visits 2 (V2) and 3 (V3) (as unblinded staff) is excluded from further contacts with trial subjects and from participating in the trial.
After the visit, the investigator enters its results into the medical documentation and the e-CRF system.
In the medical records of visit 3 (written and electronic), the result of randomization is not disclosed.
After visit 3, the division of subjects into Groups II and III (randomisation) is recorded only in separate written records; the physician participating in visit 2 and 3 sends the documentation to the leading centre after the end of visit 3, where it is stored and fully protected against access of blinded personnel.
The subject must not be informed about the group he/she belongs to.
入排标准
- 年龄范围
- 25 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •a health care professional (physician, nurse, midwife, paramedic, electroradiology technician, laboratory diagnostician, physiotherapist, nutritionist, orderly) aged >25 years
- •no confirmed SARS-CoV-2 infection
- •informed consent to participate in the trial and consent to personal data processing
- •declared availability for telephone contacts throughout the study period
- •good health condition
- •earlier vaccination against tuberculosis
排除标准
- •hypersensitivity to any component of BCG-10
- •hypersensitivity to previously administered tuberculin (local skin lesions, necrosis of the skin, blisters, other severe skin reactions at the injection site)
- •HIV infection (confirmed or suspected infections, even if they are asymptomatic)
- •primary or secondary immunodeficiencies (including interferon - gamma deficiency or DiGeorge syndrome)
- •radiotherapy (less than 24 months before the date of inclusion in the trial
- •treatment with corticosteroids, ongoing immunosuppressive therapy (including those treated with monoclonal antibodies to TNF-α, such as infliximab) - less than 24 months before the date of inclusion in the trial
- •neoplastic diseases (e.g. leukaemia, malignant granuloma, lymphoma or some other cancer of the reticuloendothelial system) - less than 24 months before the date of inclusion in the study
- •after stem cell transplantation and organ transplantation
- •in the exacerbation stage of chronic diseases (including severe malnutrition)
- •pregnancy
- •history of tuberculosis
- •keloid at the vaccination site after previous BCG vaccination
研究组 & 干预措施
Group II
with negative RT23 test reading, receiving BCG-10 Vaccine
干预措施: BCG-10 vaccine (Drug)
Group III
with negative RT23 test reading, receiving placebo
干预措施: 0.9% saline (Drug)
结局指标
主要结局
death and life- or health-threatening condition (cardiac arrest with effective resuscitation, shock, severe respiratory failure, severe renal failure, stroke/transient cerebral ischaemia)
时间窗: throughout the period of 18 months from inclusion
* shock - when catecholamines are required despite initial fluid resuscitation * severe respiratory failure - the need for non-invasive or invasive ventilation * severe renal failure - the need for renal replacement therapy (for undialysed individuals, i.e. with end-stage renal failure (ESRD)
次要结局
- Onset of clinical symptoms of COVID-19(12 weeks from the date of the third visit - V3)
- asymptomatic SARS-CovV-2 infection(12 weeks from the date of the third visit - V3)
- Hospitalisation(12 weeks from the date of the third visit - V3)
- ICU Hospitalisation(12 weeks from the date of the third visit - V3)
- Dyspnoea(12 weeks from the date of the third visit - V3)
研究者
Hanna Czajka
National Project Coordinator
University of Rzeszow