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BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04327206
Recruitment Status : Recruiting
First Posted : March 31, 2020
Last Update Posted : February 5, 2021
Sponsor:
Collaborator:
Royal Children's Hospital
Information provided by (Responsible Party):
Murdoch Childrens Research Institute

Tracking Information
First Submitted Date  ICMJE March 25, 2020
First Posted Date  ICMJE March 31, 2020
Last Update Posted Date February 5, 2021
Actual Study Start Date  ICMJE March 30, 2020
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • COVID-19 disease incidence [ Time Frame: Measured over the 6 months following randomisation ]
    Number of participants with COVID-19 disease defined as
    • positive SARS-Cov-2 test (PCR, antigen 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 disease incidence [ Time Frame: Measured over the 6 months following randomisation ]
    Number of participants with severe COVID-19 disease, defined as: COVID-19 disease with hospitalisation, death, or non-hospitalised severe disease. Non-hospitalised severe disease is defined as non-ambulant (*) for ≥ 3 consecutive days OR 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"
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • COVID-19 disease incidence [ Time Frame: Measured over the 6 months following randomisation ]
    Number of participants with COVID-19 disease defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • Severe COVID-19 disease incidence [ Time Frame: Measured over the 6 months following randomisation ]
    Number of participants who were admitted to hospital or died (using self-reported questionnaire and/or medical/hospital records) in the context of a positive SARS-CoV-2 test
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • COVID-19 incidence by 12 months [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with COVID-19 disease defined as
    • positive SARS-Cov-2 test (PCR 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 by 12 months [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with severe COVID-19 disease, defined as: COVID-19 disease with hospitalisation, death, or non-hospitalised severe disease. Non-hospitalised severe disease is defined as non-ambulant(*) for ≥ 3 consecutive days OR 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"
  • Time to first symptom of COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Time to first symptom of COVID-19 in a participant who subsequently meets the case definition:
    • positive SARS-Cov-2 test (PCR, antigen 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)
  • Episodes of COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of episodes of COVID-19 disease defined as
    • positive SARS-Cov-2 test (PCR, antigen 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)
  • Asymptomatic SARS-CoV-2 infection [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with asymptomatic SARS-CoV-2 infection defined as
    • Evidence of SARS-CoV-2 infection (by PCR or seroconversion)
    • Absence of respiratory illness (using self-reported questionnaire)
    • No evidence of exposure prior to randomisation (inclusion serology negative)
  • Work absenteeism due to COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to COVID-19 disease defined as
    • positive SARS-Cov-2 test (PCR, antigen 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)
  • Bed confinement due to COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease defined as
    • positive SARS-Cov-2 test (PCR 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)
  • Symptom duration of COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days with symptoms in any episode of illness that meets the case definition for COVID-19 disease:
    • positive SARS-Cov-2 test (PCR, antigen 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)
  • SARS-CoV-2 pneumonia [ Time Frame: Measured over the 12 months following randomisation ]
    Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Oxygen therapy with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Critical care admissions with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Critical care admission duration with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Mechanical ventilation with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
  • Mechanical ventilation duration with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
  • Hospitalisation duration with COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
  • Mortality with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of deaths (from death registry) associated with a positive SARS-CoV-2 test
  • Fever or respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with fever or respiratory illness will be defined as:
    • fever (using self-reported questionnaire), or
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Episodes of fever or respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of episodes of fever or respiratory illness, defined as
    • fever (using self-reported questionnaire), or
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Work absenteeism due to fever or respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to fever or respiratory illness defined as
    • fever (using self-reported questionnaire), or
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Bed confinement due to fever or respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days confined to bed (using self-reported questionnaire) due to fever or respiratory illness defined as
    • fever (using self-reported questionnaire), or
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Symptom duration of fever or respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days with symptoms in any episode of illness that meets the case definition for fever or respiratory illness:
    • fever (using self-reported questionnaire), or
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Pneumonia [ Time Frame: Measured over the 12 months following randomisation ]
    Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)
  • Oxygen therapy [ Time Frame: Measured over the 12 months following randomisation ]
    Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
  • Critical care admissions [ Time Frame: Measured over the 12 months following randomisation ]
    Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
  • Mechanical ventilation [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
  • Mortality [ Time Frame: Measured over the 12 months following randomisation ]
    Number of deaths (from death registry)
  • Hospitalisation duration with fever or respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days of hospitalisation due to fever or respiratory illness (using self-reported questionnaire, medical/hospital records and/or government registries)
  • Unplanned work absenteeism [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
  • Local and systemic adverse events to BCG vaccination in healthcare workers [ Time Frame: Measured over the 3 months following randomisation ]
    Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2020)
  • COVID-19 incidence by 12 months [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with COVID-19 disease defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • Severe COVID-19 incidence by 12 months [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with severe COVID-19 disease defined as hospitalisation or death in the context of a positive SARS-Cov-2 test (PCR or serology)
  • Time to first symptom of COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Time to first symptom of COVID-19 in a participant who subsequently meets the case definition:
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • Episodes of COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of episodes of COVID-19 disease defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • Asymptomatic SARS-CoV-2 infection [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with asymptomatic SARS-CoV-2 infection defined as
    • Evidence of SARS-CoV-2 infection (by PCR or seroconversion)
    • Absence of respiratory illness (using self-reported questionnaire)
    • No evidence of exposure prior to randomisation (inclusion serology negative)
  • Work absenteeism due to COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to COVID-19 disease defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • Bed confinement due to COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • Symptom duration of COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days with symptoms in any episode of illness that meets the case definition for COVID-19 disease:
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
    • positive SARS-Cov-2 test (PCR or serology)
  • SARS-CoV-2 pneumonia [ Time Frame: Measured over the 12 months following randomisation ]
    Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Oxygen therapy with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Critical care admissions with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Critical care admission duration with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
  • Mechanical ventilation with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
  • Mechanical ventilation duration with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
  • Hospitalisation duration with COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
  • Mortality with SARS-CoV-2 [ Time Frame: Measured over the 12 months following randomisation ]
    Number of deaths (from death registry) associated with a positive SARS-CoV-2 test
  • Febrile respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants with febrile respiratory illness defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Episodes of febrile respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of episodes of febrile respiratory illness, defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Work absenteeism due to febrile respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to febrile respiratory illness defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Bed confinement due to febrile respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days confined to bed (using self-reported questionnaire) due to febrile respiratory illness defined as
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Symptom duration of febrile respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days with symptoms in any episode of illness that meets the case definition for febrile respiratory illness:
    • fever (using self-reported questionnaire), plus
    • at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
  • Pneumonia [ Time Frame: Measured over the 12 months following randomisation ]
    Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)
  • Oxygen therapy [ Time Frame: Measured over the 12 months following randomisation ]
    Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
  • Critical care admissions [ Time Frame: Measured over the 12 months following randomisation ]
    Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
  • Mechanical ventilation [ Time Frame: Measured over the 12 months following randomisation ]
    Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
  • Mortality [ Time Frame: Measured over the 12 months following randomisation ]
    Number of deaths (from death registry)
  • Hospitalisation duration with febrile respiratory illness [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days of hospitalisation due to febrile respiratory illness (using self-reported questionnaire and/or medical/hospital records)
  • Unplanned work absenteeism [ Time Frame: Measured over the 12 months following randomisation ]
    Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
  • Hospitalisation cost to treat COVID-19 [ Time Frame: Measured over the 12 months following randomisation ]
    Cost of hospitalisation due to COVID-19 reported in Australian dollars (using hospital administrative linked costing records held by individual hospitals and state government routine costing data collections to provide an estimate of the cost to hospitals for each episode of COVID-19 care)
  • Local and systemic adverse events to BCG vaccination in healthcare workers [ Time Frame: Measured over the 3 months following randomisation ]
    Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BCG Vaccination to Protect Healthcare Workers Against COVID-19
Official Title  ICMJE BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers (BRACE) Trial
Brief Summary 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.
Detailed Description

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 first phase of this study, where participants were randomised to receive BCG or no BCG vaccine at the time of receiving influenza vaccination.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Phase III, two group, multicentre, randomised controlled trial
Masking: Double (Participant, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Prevention
Condition  ICMJE
  • Coronavirus Disease 2019 (COVID-19)
  • Respiratory Illness
  • Corona Virus Infection
  • COVID-19
Intervention  ICMJE
  • Drug: BCG Vaccine

    Freeze-dried powder: Live attenuated strain of Mycobacterium bovis (BCG), Danish strain 1331.

    Each 0.1 ml vaccine contains between 200000 to 800000 colony forming units. Adult dose is 0.1 ml given by intradermal injection

    Other Names:
    • Bacille Calmette-Guerin Vaccine
    • Bacillus Calmette-Guerin Vaccine
    • Statens Serum Institute BCG vaccine
    • Mycobacterium bovis BCG (Bacille Calmette Guérin), Danish Strain 1331
    • BCG Denmark
  • Drug: 0.9%NaCl
    0.9% Sodium Chloride Injection
    Other Name: 0.9% Saline
Study Arms  ICMJE
  • Experimental: 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).
    Intervention: Drug: BCG Vaccine
  • Placebo Comparator: 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).
    Intervention: Drug: 0.9%NaCl
Publications * Crisan-Dabija R, Grigorescu C, Pavel CA, Artene B, Popa IV, Cernomaz A, Burlacu A. Tuberculosis and COVID-19: Lessons from the Past Viral Outbreaks and Possible Future Outcomes. Can Respir J. 2020 Sep 5;2020:1401053. doi: 10.1155/2020/1401053. eCollection 2020. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 17, 2020)		 10078
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2020)		 4170
Estimated Study Completion Date  ICMJE March 30, 2022
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

    • Pregnant

      • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Prof Nigel Curtis, MBBS PhD +613 93456366 nigel.curtis@rch.org.au
Listed Location Countries  ICMJE Australia,   Brazil,   Netherlands,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04327206
Other Study ID Numbers  ICMJE 62586
U1111-1256-4104 ( Registry Identifier: The Universal Trial Number (UTN) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Beginning 6 months following analysis and article publications, the following may be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions, under a collaborator agreement, for accessing:

  • Individual participant data that underlie the results reported in our articles after de-identification (text, tables, figures and appendices)
  • Study protocol, Statistical Analysis Plan, Participant Informed Consent Form (PICF)
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Beginning 6 months following analysis and article publications, for long-term use
Access Criteria: Researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions, under a collaborator agreement
Responsible Party Murdoch Childrens Research Institute
Study Sponsor  ICMJE Murdoch Childrens Research Institute
Collaborators  ICMJE Royal Children's Hospital
Investigators  ICMJE
Principal Investigator: Prof Nigel Curtis Murdoch Children's Research Institute
PRS Account Murdoch Childrens Research Institute
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP