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BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers Following Coronavirus Exposure (BRACE) Trial

Trial Profile

BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers Following Coronavirus Exposure (BRACE) Trial

Status: Recruiting
Phase of Trial: Phase III

Latest Information Update: 28 May 2020

At a glance

  • Drugs BCG vaccine (Primary)
  • Indications COVID 2019 infections
  • Focus Adverse reactions
  • Acronyms BRACE
  • Most Recent Events

    • 17 May 2020 Outcome measures, arm, study design and eligibility criteria amended.
    • 17 May 2020 Planned number of patients changed from 4170 to 10078.
    • 02 Apr 2020 New trial record

Trial Overview

Purpose

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.

Primary Endpoints

COVID-19 disease incidence

description: 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)
time_frame: Measured over the 6 months following randomisation

Severe COVID-19 disease incidence

description: 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_frame: Measured over the 6 months following randomisation

Other Endpoints

COVID-19 incidence by 12 months

description: 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)
time_frame: Measured over the 12 months following randomisation

Severe COVID-19 incidence by 12 months

description: 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_frame: Measured over the 12 months following randomisation

Time to first symptom of COVID-19

description: Time to first symptom of COVID-19 in a participant who subsequently meets the case definition:
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)
time_frame: Measured over the 12 months following randomisation

Episodes of COVID-19

description: Number of episodes of 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)
time_frame: Measured over the 12 months following randomisation

Asymptomatic SARS-CoV-2 infection

description: 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)
time_frame: Measured over the 12 months following randomisation

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 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)
time_frame: Measured over the 12 months following randomisation

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 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

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 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

SARS-CoV-2 pneumonia

description: 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
time_frame: Measured over the 12 months following randomisation

Oxygen therapy with SARS-CoV-2

description: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
time_frame: Measured over the 12 months following randomisation

Critical care admissions with SARS-CoV-2

description: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
time_frame: Measured over the 12 months following randomisation

Critical care admission duration with SARS-CoV-2

description: Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
time_frame: Measured over the 12 months following randomisation

Mechanical ventilation with SARS-CoV-2

description: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
time_frame: Measured over the 12 months following randomisation

Mechanical ventilation duration with SARS-CoV-2

description: Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
time_frame: Measured over the 12 months following randomisation

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 12 months following randomisation

Mortality with SARS-CoV-2

description: Number of deaths (from death registry) associated with a positive SARS-CoV-2 test
time_frame: Measured over the 12 months following randomisation

Fever or respiratory illness

description: 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)
time_frame: Measured over the 12 months following randomisation

Episodes of fever or respiratory illness

description: 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)
time_frame: Measured over the 12 months following randomisation

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

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

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

Pneumonia

description: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)
time_frame: Measured over the 12 months following randomisation

Oxygen therapy

description: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
time_frame: Measured over the 12 months following randomisation

Critical care admissions

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

Mechanical ventilation

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

Mortality

description: Number of deaths (from death registry)
time_frame: Measured over the 12 months following randomisation

Hospitalisation duration with fever or respiratory illness

description: Number of days of hospitalisation due to fever or respiratory illness (using self-reported questionnaire, medical/hospital records and/or government registries)
time_frame: Measured over the 12 months following randomisation

Unplanned work absenteeism

description: Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
time_frame: Measured over the 12 months following randomisation

Hospitalisation cost to treat COVID-19

description: Cost of hospitalisation due to COVID-19 will be reported and compared between groups (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)
time_frame: Measured over the 12 months following randomisation

Local and systemic adverse events to BCG vaccination in healthcare workers

description: Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.
time_frame: Measured over the 3 months following randomisation [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections prevention -

Subjects

  • Subject Type patients
  • Number

    Planned: 10078

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

- Over 18 years of age - In Europe: Healthcare worker who over the next few months of COVID-19 pandemic will be working onsite in patient areas or having face-to-face contact with patients. -Note that this may include staff in either hospitals or other patient care facilities, such as nursing homes. Proof of registration as patient care worker will be required at enrolment. - In Australia: Employed by one of the hospitals involved in the study - Note that this is not restricted to clinicians or nurses and include all individuals who work within the participating hospital during the COVID-19 outbreak. - Provide a signed and dated informed consent form - Has received the influenza vaccine at least 72 hours prior to randomisation - Note that this criteria only applies in to Australian participants - Pre-randomisation blood collected

Patient 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 (more than or equal to 20 mg for more than or equal to 2 weeks), non-biological immunosuppressant (also known as 'DMARDS'), biological agents (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha). - Has a congenital cellular immunodeficiency, including specific deficiencies of the interferon-gamma pathway - Has a malignancy involving bone marrow or lymphoid systems - Has any serious underlying illness (such as malignancy). Please note: People with cardiovascular disease, hypertension, diabetes, and/or chronic respiratory disease are eligible if not immunocompromised - Known or suspected HIV infection, even if asymptomatic or has normal immune function. This is because of the risk of disseminated BCG infection - Has active skin disease such as eczema, dermatitis or psoriasis at or near the site of vaccination. A different site (other than left 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. - 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 ingredient present in the BCG vaccine - Previous active tuberculosis (TB) disease - Previous adverse reaction to BCG vaccine (significant local reaction (abscess) or suppurative lymphadenitis) - BCG vaccine given within the last year - Has previously had a SARS-CoV-2 positive test result - Already part of this trial, recruited at a different hospital - Participation in another COVID-19 prevention trial

Trial Details

Identifiers

Identifier Owner
NCT04327206 ClinicalTrials.gov: US National Institutes of Health
62586 -

Trial Dates

  • Initiation Dates

    Planned : 30 Mar 2020

    Actual : 30 Mar 2020

  • Primary Completion Dates

    Planned : 30 Oct 2020

  • End Dates

    Planned : 30 Mar 2022

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location Australia
  • Focus Adverse reactions

Interventions

Drugs Route Formulation
BCG vaccinePrimary Drug Intradermal Injection

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). 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 Name: Bacille Calmette-Guerin Vaccine, Bacillus Calmette-Guerin Vaccine, Statens Serum Institute BCG vaccine, Mycobacterium bovis BCG (Bacille Calmette Guérin), Danish Strain 1331, BCG Denmark

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). Drug: 0.9%NaCl (0.9% Sodium Chloride Injection) Other Name: 0.9% Saline

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
A/Prof Jeffrey Post, MBBS PhD
+61 2 93823405
show details
Prince of Wales Hospital Australia
A/Prof Mark Douglas, MBBS PhD
+61 2 8890 6012 mark.douglas@sydney.edu.au
show details
Westmead Hospital Australia
A/Prof Nicholas Wood, MBBS PhD
+61 2 9845 0000 nicholas.wood@health.nsw.gov.au
show details
The Children's Hospital at Westmead Australia
A/Prof Tony Korman, MBBS FRACP
+61 3 9594 4533 tony.korman@monash.edu
show details
Monash Health- Monash Medical Centre Australia
Dr Anthony Byrne, MBBS PhD
+61 2 8382 1111 anthony.byrne@svha.org.au
show details
St Vincent's Hospital, Sydney Australia
Dr Brendan McMullan, BMed, FRACP
+61 2 9382 1111 brendan.mcmullan@health.nsw.gov.au
show details
Sydney Children's Hospital, Randwick Australia
Dr Nicole Tan, MBBS FANZCA
+61 3 9427 7899 niki.tan@anaestheticservices.com.au
show details
Epworth Eastern, Epworth Richmond, Epworth Victoria Parade Australia
Dr Simone Barry, MBBS PhD
+61 8 7074 0000 simone.barry@sa.gov.au
show details
Royal Adelaide Hospital Australia
Kaya Gardiner
+613 99366461 kaya.gardiner@mcri.edu.au
show details
-
Prof David Lynn, PhD
+61 8 8128 4053 david.lynn@sahmri.com
show details
South Australian Health and Medical Research Institute Australia
Prof Helen Marshall, MBBS MD MPH
+61 8 8161 8115 helen.marshall@adelaide.edu.au
show details
Women's and Children's Hospital Australia
Prof Nigel Curtis Murdoch Children's Research Institute
-
Prof Nigel Curtis, MBBS PhD
+613 93456366 nigel.curtis@rch.org.au
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Epworth Eastern Melbourne, Victoria Australia
Epworth Richmond Melbourne, Victoria Australia
Epworth Victoria Parade Melbourne, Victoria Australia
Fiona Stanley Hospital Murdoch, Western Australia Australia
Monash Health- Monash Medical Centre Melbourne, Victoria Australia
Murdoch Children's Research Institute
-
-
Murdoch Childrens Research Institute
-
-
Perth Children's Hospital Perth, Western Australia Australia
Prince of Wales Hospital Sydney, New South Wales Australia
Royal Adelaide Hospital Adelaide, South Australia Australia
Royal Children's Hospital
-
-
Royal Children's Hospital Melbourne, Victoria Australia
Sir Charles Gairdner Hospital Perth, Western Australia Australia
South Australian Health and Medical Research Institute Adelaide, South Australia Australia
St Vincent's Hospital, Sydney Sydney, New South Wales Australia
Sydney Children's Hospital, Randwick Sydney, New South Wales Australia
The Children's Hospital at Westmead Sydney, New South Wales Australia
Westmead Hospital Sydney, New South Wales Australia
Women's and Children's Hospital North Adelaide, South Australia Australia

Trial History

Event Date Event Type Comment
28 May 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 28 May 2020
17 May 2020 Protocol amendment Outcome measures, arm, study design and eligibility criteria amended. Updated 20 May 2020
17 May 2020 Other trial event Planned number of patients changed from 4170 to 10078. Updated 20 May 2020
02 Apr 2020 New trial record New trial record Updated 02 Apr 2020
01 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 06 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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