BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers (BRACE) Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 6,828
- 试验地点
- 36
- 主要终点
- Symptomatic COVID-19 by 6 months
研究概览
简要总结
Phase III, two-group multicentre, randomised controlled trial in up to 10 078 healthcare workers to determine if BCG vaccination reduces the incidence and severity of COVID-19 during the 2020 pandemic.
详细描述
Healthcare workers are at the frontline of the coronavirus disease (COVID-19) pandemic. They will be randomised to receive a single dose of BCG vaccine or 0.9% NaCl placebo. Participants will be followed-up for 12 months with notification from a Smartphone application or phone calls (up to daily when ill) and surveys to identify and detail COVID-19 infection. Additional information on severe disease will be obtained from hospital medical records and/or government databases. Blood samples will be collected prior to randomisation and at 3, 6, 9 and 12 months to determine exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where required, swab/blood samples will be taken at illness episodes to assess SARS-CoV-2 infection.
The trial includes a pre-planned meta-analysis with data from 2834 participants recruited in the Stage 1 of this study, where participants were randomised to receive BCG or no BCG vaccine at the time of receiving influenza vaccination.
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
The control group will receive a placebo of 0.9% sodium chloride (NaCl). Members of the research team doing the follow-up of participants and analysis will be blinded to the group allocation (by the removal of this variable and all other variables related to BCG from the dataset) until the formal detailed statistical analysis plan is confirmed and signed by all investigators and all data cleaning/preparation is complete.
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
- •Over 18 years of age
- •Healthcare worker
- •This is defined as anyone who works in a healthcare setting or has face to face contact with patients.
- •Provide a signed and dated informed consent form
- •Australian sites only: If annual influenza vaccination is available, receiving the flu vaccine is an eligibility requirement. The flu vaccine will be required a minimum of 3 days in advance of randomisation in the BRACE trial.
- •Pre-randomisation blood collected
排除标准
- •Has any BCG vaccine contraindication
- •Fever or generalised skin infection (where feasible, randomisation can be delayed until cleared)
- •Weakened resistance toward infections due to a disease in/of the immune system
- •Receiving medical treatment that affects the immune response or other immunosuppressive therapy in the last year.
- •These therapies include systemic corticosteroids (≥20 mg for ≥2 weeks), non-biological immunosuppressant (also known as 'DMARDS'), biological agents (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha).
- •People with congenital cellular immunodeficiencies, including specific deficiencies of the interferon-gamma pathway
- •People with malignancies involving bone marrow or lymphoid systems
- •People with any serious underlying illness (such as malignancy)
- •NB: People with cardiovascular disease, hypertension, diabetes, and/or chronic respiratory disease are eligible if not immunocompromised, and if they meet other eligibility criteria
- •Known or suspected HIV infection,even if they are asymptomatic or have normal immune function.
- •This is because of the risk of disseminated BCG infection
- •People with active skin disease such as eczema, dermatitis or psoriasis at or near the site of vaccination
- •A different adjacent site on the upper arm can be chosen if necessary
- •Although there is no evidence that BCG vaccination is harmful during pregnancy, it is a contra-indication to BCG vaccination. Therefore, we will exclude women who think they could be pregnant or are planning to become pregnant within the next month.
- •UK specific: Although there is no evidence that BCG vaccination is harmful during pregnancy, it is a contra-indication to BCG vaccination. Therefore, we will exclude women of childbearing potential (WOCBP) who think they could be pregnant.
- •Spain specific: If the patient is female, and of childbearing potential, she must have a negative pregnancy test at the time of inclusion and practice a reliable method of birth control for 30 days after receiving the BCG vaccination.
- •Another live vaccine administered in the month prior to randomisation
- •Require another live vaccine to be administered within the month following BCG randomisation
- •If the other live vaccine can be given on the same day, this exclusion criteria does not apply
- •Known anaphylactic reaction to any of the ingredients present in the BCG vaccine
- •Previous active TB disease
- •Currently receiving long term (more than 1 month) treatment with isoniazid, rifampicin or quinolone as these antibiotics have activity against Mycobacterium bovis
- •Previous adverse reaction to BCG vaccine (significant local reaction (abscess) or suppurative lymphadenitis)
- •BCG vaccine given within the last year
- •Have previously had a SARS-CoV-2 positive test result (positive PCR on a respiratory sample or a positive SARS-CoV-2 diagnostic antigen test approved by the local jurisdiction's public health policy)
- •Already part of this trial, recruited at a different site/hospital.
- •Participation in another COVID-19 prevention trial
- •Have previously received a COVID-19-specific vaccine
研究组 & 干预措施
BCG vaccine
Participants will receive a single dose of BCG vaccine (BCG-Denmark). The adult dose of BCG vaccine is 0.1 mL injected intradermally over the distal insertion of the deltoid muscle onto the humerus (approximately one third down the upper arm).
干预措施: BCG Vaccine (Drug)
0.9% Saline
Participants will receive a single 0.1 mL dose of 0.9%NaCl injected intradermally over the distal insertion of the deltoid muscle onto the humerus (approximately one third down the upper arm).
干预措施: 0.9%NaCl (Drug)
结局指标
主要结局
Symptomatic COVID-19 by 6 months
时间窗: Measured over the 6 months following randomisation
Number of participants with Symptomatic COVID-19 defined as * positive SARS-Cov-2 test (PCR, RAT or serology), plus * fever (using self-reported questionnaire), or * at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Severe COVID-19 incidence over 6 months
时间窗: Measured over the 6 months following randomisation
Number of participants with severe COVID-19 defined as: * positive SARS-CoV-2 test (PCR, RAT or serology), PLUS * death as a consequence of COVID-19, OR * Hospitalised as a consequence of COVID-19, OR * Non-hospitalised severe disease as a consequence of COVID-19, defined as non- ambulant\* for ≥ 3 consecutive days unable to work\*\* for ≥ 3 consecutive days (\*) "pretty much confined to bed (meaning finding it very difficult to do any normal daily activities". (\*\*) "I do not feel physically well enough to go to work"
次要结局
- Critical care admissions due to COVID-19(Measured over the 6 and 12 months following randomisation)
- Hospitalisation duration with COVID-19(Measured over the 6 and 12 months following randomisation)
- Number of Episodes of COVID-19(Measured over the 6 and 12 months following randomisation)
- Work absenteeism due to COVID-19(Measured within 6 and 12 months following randomisation)
- Symptom duration of COVID-19(Measured over 6 and12 months following randomisation)
- Time to first symptom of COVID-19(Measured over the 6 and 12 months following randomisation)
- Asymptomatic SARS-CoV-2 infection(Measured over the 6 and 12 months following randomisation)
- Oxygen therapy for a febrile or respiratory illness(Measured over the 12 months following randomisation)
- Symptomatic COVID-19 by 12 months(Measured over the 12 months following randomisation)
- Severe COVID-19 incidence over 12 months(Measured over the 12 months following randomisation)
- Bed confinement due to COVID-19(Measured over 6 and 12 months following randomisation)
- Mortality due to COVID-19(Measured over the 6 and 12 months following randomisation)
- Unplanned work absenteeism for an acute illness or hospitalisation(Measured over the 6 and 12 months following randomisation)
- Pneumonia due to COVID-19(Measured over the 6 and 12 months following randomisation)
- Oxygen therapy due to COVID-19(Measured over the 6 and12 months following randomisation)
- Mechanical ventilation due to COVID-19(Measured over the 12 months following randomisation)
- Work absenteeism due to fever or respiratory illness(Measured over the 12 months following randomisation)
- Symptom duration of fever or respiratory illness(Measured over the 12 months following randomisation)
- Pneumonia within a febrile or respiratory illness(Measured over the 12 months following randomisation)
- Mechanical ventilation for a febrile or respiratory illness(Measured over the 12 months following randomisation)
- Serious Adverse Events (SAEs) to BCG vaccination in healthcare workers(Measured over the 3 months following randomisation)
- Local and systemic adverse events to BCG vaccination in healthcare workers(Measured over the 3 months following randomisation)
- Fever or respiratory illness(Measured over the 12 months following randomisation)
- Critical care admissions for a febrile or respiratory illness(Measured over the 12 months following randomisation)
- Hospitalisation duration for a febrile or respiratory illness(Measured within 6 and 12 months following randomisation)
- Severe fever or respiratory illness(Measured over the 12 months following randomisation)
- Episodes of fever or respiratory illness(Measured over the 12 months following randomisation)
- Bed confinement due to fever or respiratory illness(Measured over the 12 months following randomisation)
- Mortality as a consequence of an episode of fever or respiratory illness(Measured over the 12 months following randomisation)