March 25, 2020
|
March 31, 2020
|
February 5, 2021
|
March 30, 2020
|
June 30, 2021 (Final data collection date for primary outcome measure)
|
- 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"
|
|
|
- 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.
|
- 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.
|
Not Provided
|
Not Provided
|
|
BCG Vaccination to Protect Healthcare Workers Against COVID-19
|
BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers (BRACE) Trial
|
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.
|
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.
|
Interventional
|
Phase 3
|
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
|
- Coronavirus Disease 2019 (COVID-19)
- Respiratory Illness
- Corona Virus Infection
- COVID-19
|
|
- 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
|
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.
|
|
Recruiting
|
10078
|
4170
|
March 30, 2022
|
June 30, 2021 (Final data collection date for primary outcome measure)
|
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:
|
Sexes Eligible for Study: |
All |
|
18 Years and older (Adult, Older Adult)
|
Yes
|
|
Australia, Brazil, Netherlands, Spain, United Kingdom
|
|
|
NCT04327206
|
62586 U1111-1256-4104 ( Registry Identifier: The Universal Trial Number (UTN) )
|
Not Provided
|
Studies a U.S. FDA-regulated Drug Product: |
No |
Studies a U.S. FDA-regulated Device Product: |
No |
|
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 |
|
Murdoch Childrens Research Institute
|
Murdoch Childrens Research Institute
|
Royal Children's Hospital
|
Principal Investigator: |
Prof Nigel Curtis |
Murdoch Children's Research Institute |
|
Murdoch Childrens Research Institute
|
February 2021
|