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

Primary Purpose

Coronavirus Disease 2019 (COVID-19), Respiratory Illness, Corona Virus Infection

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BCG Vaccine
0.9%NaCl
Sponsored by
Murdoch Childrens Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Coronavirus Disease 2019 (COVID-19)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • St Vincent's Hospital, Sydney
  • Prince of Wales Hospital
  • Sydney Children's Hospital, Randwick
  • The Children's Hospital at Westmead
  • Westmead Hospital
  • Royal Adelaide Hospital
  • Women's and Children's Hospital
  • Royal Children's Hospital
  • Epworth Richmond
  • Monash Health- Monash Medical Centre
  • Fiona Stanley Hospital
  • Perth Children's Hospital
  • Sir Charles Gairdner Hospital
  • Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD)
  • Santa Casa Hospital
  • CASSEMS Hospital
  • Federal University of Mato Grosso do Sul
  • Hospital Regional de Mato Grosso do Sul
  • Centro de Estudos da Saúde do Trabalhador e Ecologia Humana
  • Centro de Referência Prof Hélio Fraga
  • Noord West Ziekenhuis
  • Rijnstate Hospital
  • Amphia Hospital
  • St Antonius Hospital
  • Radboud UMC
  • University hospital in Utrecht (UMCU)
  • University Hospital German Trias I Pujol
  • Mutua Terrassa Univeristy Hospital
  • University Hospital Cruces
  • Marqués de Valdecilla University Hospital
  • University Hospital Virgen Macarena
  • Teign Estuary Medical Group
  • Ide Lane Surgery
  • St Leonard's Practice
  • Travel Clinic
  • Royal Devon and Exeter NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BCG vaccine

0.9% Saline

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Symptomatic COVID-19 by 6 months
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
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"

Secondary Outcome Measures

Symptomatic COVID-19 by 12 months
Number of participants symptomatic COVID-19 disease 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 12 months
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"
Time to first symptom of COVID-19
Participants who had either a symptomatic or severe COVID-19 episode will have time to first symptom of COVID-19 calculated as: [Date of any symptom onset for the first symptomatic or severe COVID-19 episode - Date of randomisation] Participants who have not had a symptomatic or severe COVID-19 episode will have time calculated as: [Earliest censoring date - date of randomisation]
Number of Episodes of COVID-19
The total number of symptomatic or severe COVID-19 episodes (refer to outcome 3 and 4 for definitions)
Asymptomatic SARS-CoV-2 infection
Number of participants with asymptomatic SARS-CoV-2 infection defined as Evidence of SARS-CoV-2 infection (by seroconversion) Absence of respiratory illness (defined by trigger or non-trigger symptoms)(using self- reported questionnaire) No evidence of exposure prior to randomisation
Work absenteeism due to COVID-19
Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to 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)
Bed confinement due to COVID-19
Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease 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)
Symptom duration of COVID-19
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, 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)
Pneumonia due to COVID-19
Number of pneumonia cases (using self-reported questionnaire and/or medical/hospital records) due to COVID-19
Oxygen therapy due to COVID-19
Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) due to COVID-19
Critical care admissions due to COVID-19
Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) due to COVID-19
Mechanical ventilation due to COVID-19
Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Hospitalisation duration with COVID-19
Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
Mortality due to COVID-19
Number of deaths due to COVID-19
Fever or respiratory illness
Respiratory illness using self-reported questionnaire defined as: at least one sign or symptom of respiratory disease including cough, sore throat, shortness of breath, respiratory distress/failure, or runny/blocked nose (in combination with another respiratory symptom or fever).
Severe fever or respiratory illness
Severe fever or respiratory illness using self-reported questionnaire defined as: Death, or Hospitalised, or Non-hospitalised severe disease, defined as non-ambulant1 for ≥ 3 consecutive days or unable to work2 for ≥ 3 consecutive days
Episodes of fever or respiratory illness
Respiratory illness using self-reported questionnaire defined as: at least one sign or symptom of respiratory disease including cough, sore throat, shortness of breath, respiratory distress/failure, or runny/blocked nose (in combination with another respiratory symptom or fever).
Work absenteeism due to fever or respiratory illness
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
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
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 within a febrile or respiratory illness
Number of pneumonia cases(using self-reported questionnaire and/or medical/hospital records)
Oxygen therapy for a febrile or respiratory illness
Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
Critical care admissions for a febrile or respiratory illness
Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
Mechanical ventilation for a febrile or respiratory illness
Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Mortality as a consequence of an episode of fever or respiratory illness
Number of deaths
Hospitalisation duration for a febrile or respiratory illness
Number of days of hospitalisation due to fever or respiratory illness (using self-reported questionnaire, medical/hospital records)
Unplanned work absenteeism for an acute illness or hospitalisation
Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
Local and systemic adverse events to BCG vaccination in healthcare workers
Adverse events (AEs), over the 3 months following randomisation, by type, severity (graded using toxicity grading scale), relationship to intervention of adverse events (AEs) of interest.
Serious Adverse Events (SAEs) to BCG vaccination in healthcare workers
SAEs over the 3 months following randomisation, by type, severity (graded using toxicity grading scale), relationship to intervention.

Full Information

First Posted
March 25, 2020
Last Updated
August 29, 2022
Sponsor
Murdoch Childrens Research Institute
Collaborators
Royal Children's Hospital, Bill and Melinda Gates Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04327206
Brief Title
BCG Vaccination to Protect Healthcare Workers Against COVID-19
Acronym
BRACE
Official Title
BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers (BRACE) Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
March 30, 2020 (Actual)
Primary Completion Date
November 10, 2021 (Actual)
Study Completion Date
May 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Murdoch Childrens Research Institute
Collaborators
Royal Children's Hospital, Bill and Melinda Gates Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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 Stage 1 of this study, where participants were randomised to receive BCG or no BCG vaccine at the time of receiving influenza vaccination.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Disease 2019 (COVID-19), Respiratory Illness, Corona Virus Infection, COVID-19

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Phase III, two group, multicentre, randomised controlled trial
Masking
ParticipantOutcomes 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.
Allocation
Randomized
Enrollment
6828 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BCG vaccine
Arm Type
Experimental
Arm Description
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).
Arm Title
0.9% Saline
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
BCG Vaccine
Other Intervention Name(s)
Bacille Calmette-Guerin Vaccine, Bacillus Calmette-Guerin Vaccine, Statens Serum Institute BCG vaccine, Mycobacterium bovis BCG (Bacille Calmette Guérin), Danish Strain 1331, BCG Denmark
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
0.9%NaCl
Other Intervention Name(s)
0.9% Saline
Intervention Description
0.9% Sodium Chloride Injection
Primary Outcome Measure Information:
Title
Symptomatic COVID-19 by 6 months
Description
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)
Time Frame
Measured over the 6 months following randomisation
Title
Severe COVID-19 incidence over 6 months
Description
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"
Time Frame
Measured over the 6 months following randomisation
Secondary Outcome Measure Information:
Title
Symptomatic COVID-19 by 12 months
Description
Number of participants symptomatic COVID-19 disease 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)
Time Frame
Measured over the 12 months following randomisation
Title
Severe COVID-19 incidence over 12 months
Description
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"
Time Frame
Measured over the 12 months following randomisation
Title
Time to first symptom of COVID-19
Description
Participants who had either a symptomatic or severe COVID-19 episode will have time to first symptom of COVID-19 calculated as: [Date of any symptom onset for the first symptomatic or severe COVID-19 episode - Date of randomisation] Participants who have not had a symptomatic or severe COVID-19 episode will have time calculated as: [Earliest censoring date - date of randomisation]
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Number of Episodes of COVID-19
Description
The total number of symptomatic or severe COVID-19 episodes (refer to outcome 3 and 4 for definitions)
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Asymptomatic SARS-CoV-2 infection
Description
Number of participants with asymptomatic SARS-CoV-2 infection defined as Evidence of SARS-CoV-2 infection (by seroconversion) Absence of respiratory illness (defined by trigger or non-trigger symptoms)(using self- reported questionnaire) No evidence of exposure prior to randomisation
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Work absenteeism due to COVID-19
Description
Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to 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)
Time Frame
Measured within 6 and 12 months following randomisation
Title
Bed confinement due to COVID-19
Description
Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease 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)
Time Frame
Measured over 6 and 12 months following randomisation
Title
Symptom duration of COVID-19
Description
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, 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)
Time Frame
Measured over 6 and12 months following randomisation
Title
Pneumonia due to COVID-19
Description
Number of pneumonia cases (using self-reported questionnaire and/or medical/hospital records) due to COVID-19
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Oxygen therapy due to COVID-19
Description
Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) due to COVID-19
Time Frame
Measured over the 6 and12 months following randomisation
Title
Critical care admissions due to COVID-19
Description
Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) due to COVID-19
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Mechanical ventilation due to COVID-19
Description
Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Time Frame
Measured over the 12 months following randomisation
Title
Hospitalisation duration with COVID-19
Description
Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Mortality due to COVID-19
Description
Number of deaths due to COVID-19
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Fever or respiratory illness
Description
Respiratory illness using self-reported questionnaire defined as: at least one sign or symptom of respiratory disease including cough, sore throat, shortness of breath, respiratory distress/failure, or runny/blocked nose (in combination with another respiratory symptom or fever).
Time Frame
Measured over the 12 months following randomisation
Title
Severe fever or respiratory illness
Description
Severe fever or respiratory illness using self-reported questionnaire defined as: Death, or Hospitalised, or Non-hospitalised severe disease, defined as non-ambulant1 for ≥ 3 consecutive days or unable to work2 for ≥ 3 consecutive days
Time Frame
Measured over the 12 months following randomisation
Title
Episodes of fever or respiratory illness
Description
Respiratory illness using self-reported questionnaire defined as: at least one sign or symptom of respiratory disease including cough, sore throat, shortness of breath, respiratory distress/failure, or runny/blocked nose (in combination with another respiratory symptom or fever).
Time Frame
Measured over the 12 months following randomisation
Title
Work absenteeism due to fever or respiratory illness
Description
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)
Time Frame
Measured over the 12 months following randomisation
Title
Bed confinement due to fever or respiratory illness
Description
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)
Time Frame
Measured over the 12 months following randomisation
Title
Symptom duration of fever or respiratory illness
Description
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)
Time Frame
Measured over the 12 months following randomisation
Title
Pneumonia within a febrile or respiratory illness
Description
Number of pneumonia cases(using self-reported questionnaire and/or medical/hospital records)
Time Frame
Measured over the 12 months following randomisation
Title
Oxygen therapy for a febrile or respiratory illness
Description
Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
Time Frame
Measured over the 12 months following randomisation
Title
Critical care admissions for a febrile or respiratory illness
Description
Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
Time Frame
Measured over the 12 months following randomisation
Title
Mechanical ventilation for a febrile or respiratory illness
Description
Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Time Frame
Measured over the 12 months following randomisation
Title
Mortality as a consequence of an episode of fever or respiratory illness
Description
Number of deaths
Time Frame
Measured over the 12 months following randomisation
Title
Hospitalisation duration for a febrile or respiratory illness
Description
Number of days of hospitalisation due to fever or respiratory illness (using self-reported questionnaire, medical/hospital records)
Time Frame
Measured within 6 and 12 months following randomisation
Title
Unplanned work absenteeism for an acute illness or hospitalisation
Description
Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
Time Frame
Measured over the 6 and 12 months following randomisation
Title
Local and systemic adverse events to BCG vaccination in healthcare workers
Description
Adverse events (AEs), over the 3 months following randomisation, by type, severity (graded using toxicity grading scale), relationship to intervention of adverse events (AEs) of interest.
Time Frame
Measured over the 3 months following randomisation
Title
Serious Adverse Events (SAEs) to BCG vaccination in healthcare workers
Description
SAEs over the 3 months following randomisation, by type, severity (graded using toxicity grading scale), relationship to intervention.
Time Frame
Measured over the 3 months following randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof Nigel Curtis
Organizational Affiliation
Murdoch Children's Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Vincent's Hospital, Sydney
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Prince of Wales Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Sydney Children's Hospital, Randwick
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
The Children's Hospital at Westmead
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Westmead Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Women's and Children's Hospital
City
North Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Facility Name
Royal Children's Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Epworth Richmond
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3121
Country
Australia
Facility Name
Monash Health- Monash Medical Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
Perth Children's Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD)
City
Manaus
State/Province
Amazonas
ZIP/Postal Code
69040-000
Country
Brazil
Facility Name
Santa Casa Hospital
City
Campo Grande
State/Province
Mato Grosso Do Sul
ZIP/Postal Code
79002-230
Country
Brazil
Facility Name
CASSEMS Hospital
City
Campo Grande
State/Province
Mato Grosso Do Sul
ZIP/Postal Code
79002-251
Country
Brazil
Facility Name
Federal University of Mato Grosso do Sul
City
Campo Grande
State/Province
Mato Grosso Do Sul
ZIP/Postal Code
79070-900
Country
Brazil
Facility Name
Hospital Regional de Mato Grosso do Sul
City
Campo Grande
State/Province
Mato Grosso Do Sul
ZIP/Postal Code
79084-180
Country
Brazil
Facility Name
Centro de Estudos da Saúde do Trabalhador e Ecologia Humana
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
22780-195
Country
Brazil
Facility Name
Centro de Referência Prof Hélio Fraga
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
22780-195
Country
Brazil
Facility Name
Noord West Ziekenhuis
City
Alkmaar
ZIP/Postal Code
1815 JD
Country
Netherlands
Facility Name
Rijnstate Hospital
City
Arnhem
ZIP/Postal Code
6815 AD
Country
Netherlands
Facility Name
Amphia Hospital
City
Breda
ZIP/Postal Code
4818 CK
Country
Netherlands
Facility Name
St Antonius Hospital
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
Facility Name
Radboud UMC
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
University hospital in Utrecht (UMCU)
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
University Hospital German Trias I Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Mutua Terrassa Univeristy Hospital
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08221
Country
Spain
Facility Name
University Hospital Cruces
City
Barakaldo
State/Province
Bizkaia
ZIP/Postal Code
48903
Country
Spain
Facility Name
Marqués de Valdecilla University Hospital
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
University Hospital Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Teign Estuary Medical Group
City
Teignmouth
State/Province
Devon
ZIP/Postal Code
TQ14 8AB
Country
United Kingdom
Facility Name
Ide Lane Surgery
City
Alphington
State/Province
Exeter
ZIP/Postal Code
EX2 8UP
Country
United Kingdom
Facility Name
St Leonard's Practice
City
St Leonards
State/Province
Exeter
ZIP/Postal Code
EX1 1SB
Country
United Kingdom
Facility Name
Travel Clinic
City
Exeter
ZIP/Postal Code
EX1 1PR
Country
United Kingdom
Facility Name
Royal Devon and Exeter NHS Foundation Trust
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Under the terms of the funding agreement with the Bill and Melinda Gates foundation, the BRACE trial has a data sharing agreement in place. An anonymised Individual Participant Data (IPD) dataset and a data dictionary will be provided to Vivli (https://vivli.org/) under the terms of the agreements with the Bill and Melinda Gates foundation grant and Vivli. After database lock, 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 deidentification (text, tables, figures and appendices) Study protocol, Statistical Analysis Plan, PICF
IPD Sharing Time Frame
After database lock, a 12-month embargo period will be in place, to allow adequate time for analyses and publication outputs. Data transfer to Vivli should occur during the embargo period.
IPD Sharing Access Criteria
Researchers from a recognised research institution can approach MCRI for access of data. The researcher will need to provide evidence that the proposed use of the data has been ethically reviewed and approved by an Institutional Review Board (IRB)/ Human Research Ethics Committee(HREC), and accept MCRI's conditions, under a collaborator agreement.
Citations:
PubMed Identifier
34711598
Citation
Pittet LF, Messina NL, Gardiner K, Orsini F, Abruzzo V, Bannister S, Bonten M, Campbell JL, Croda J, Dalcolmo M, Elia S, Germano S, Goodall C, Gwee A, Jamieson T, Jardim B, Kollmann TR, Guimaraes Lacerda MV, Lee KJ, Legge D, Lucas M, Lynn DJ, McDonald E, Manning L, Munns CF, Perrett KP, Prat Aymerich C, Richmond P, Shann F, Sudbury E, Villanueva P, Wood NJ, Lieschke K, Subbarao K, Davidson A, Curtis N; BRACE trial Consortium Group. BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial). BMJ Open. 2021 Oct 28;11(10):e052101. doi: 10.1136/bmjopen-2021-052101.
Results Reference
derived
PubMed Identifier
32934758
Citation
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.
Results Reference
derived

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BCG Vaccination to Protect Healthcare Workers Against COVID-19

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