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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04327206




Registration number
NCT04327206
Ethics application status
Date submitted
25/03/2020
Date registered
31/03/2020
Date last updated
22/10/2020

Titles & IDs
Public title
BCG Vaccination to Protect Healthcare Workers Against COVID-19
Scientific title
BCG Vaccination to Reduce the Impact of COVID-19 in Healthcare Workers (BRACE) Trial
Secondary ID [1] 0 0
U1111-1256-4104
Secondary ID [2] 0 0
62586
Universal Trial Number (UTN)
Trial acronym
BRACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronavirus Disease 2019 (COVID-19) 0 0
Respiratory Illness 0 0
Corona Virus Infection 0 0
COVID-19 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BCG Vaccine
Treatment: Drugs - 0.9%NaCl

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).

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).


Treatment: Drugs: 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

Treatment: Drugs: 0.9%NaCl
0.9% Sodium Chloride Injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
COVID-19 disease incidence - 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)
Timepoint [1] 0 0
Measured over the 6 months following randomisation
Primary outcome [2] 0 0
Severe COVID-19 disease incidence - 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"
Timepoint [2] 0 0
Measured over the 6 months following randomisation
Secondary outcome [1] 0 0
COVID-19 incidence by 12 months - 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)
Timepoint [1] 0 0
Measured over the 12 months following randomisation
Secondary outcome [2] 0 0
Severe COVID-19 incidence by 12 months - 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"
Timepoint [2] 0 0
Measured over the 12 months following randomisation
Secondary outcome [3] 0 0
Time to first symptom of COVID-19 - 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)
Timepoint [3] 0 0
Measured over the 12 months following randomisation
Secondary outcome [4] 0 0
Episodes of COVID-19 - 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)
Timepoint [4] 0 0
Measured over the 12 months following randomisation
Secondary outcome [5] 0 0
Asymptomatic SARS-CoV-2 infection - 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)
Timepoint [5] 0 0
Measured over the 12 months following randomisation
Secondary outcome [6] 0 0
Work absenteeism due to COVID-19 - 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)
Timepoint [6] 0 0
Measured over the 12 months following randomisation
Secondary outcome [7] 0 0
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 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)
Timepoint [7] 0 0
Measured over the 12 months following randomisation
Secondary outcome [8] 0 0
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 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)
Timepoint [8] 0 0
Measured over the 12 months following randomisation
Secondary outcome [9] 0 0
SARS-CoV-2 pneumonia - 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
Timepoint [9] 0 0
Measured over the 12 months following randomisation
Secondary outcome [10] 0 0
Oxygen therapy with SARS-CoV-2 - Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Timepoint [10] 0 0
Measured over the 12 months following randomisation
Secondary outcome [11] 0 0
Critical care admissions with SARS-CoV-2 - Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Timepoint [11] 0 0
Measured over the 12 months following randomisation
Secondary outcome [12] 0 0
Critical care admission duration with SARS-CoV-2 - Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Timepoint [12] 0 0
Measured over the 12 months following randomisation
Secondary outcome [13] 0 0
Mechanical ventilation with SARS-CoV-2 - Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
Timepoint [13] 0 0
Measured over the 12 months following randomisation
Secondary outcome [14] 0 0
Mechanical ventilation duration with SARS-CoV-2 - Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
Timepoint [14] 0 0
Measured over the 12 months following randomisation
Secondary outcome [15] 0 0
Hospitalisation duration with COVID-19 - Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
Timepoint [15] 0 0
Measured over the 12 months following randomisation
Secondary outcome [16] 0 0
Mortality with SARS-CoV-2 - Number of deaths (from death registry) associated with a positive SARS-CoV-2 test
Timepoint [16] 0 0
Measured over the 12 months following randomisation
Secondary outcome [17] 0 0
Fever or respiratory illness - 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)
Timepoint [17] 0 0
Measured over the 12 months following randomisation
Secondary outcome [18] 0 0
Episodes of fever or respiratory illness - 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)
Timepoint [18] 0 0
Measured over the 12 months following randomisation
Secondary outcome [19] 0 0
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)
Timepoint [19] 0 0
Measured over the 12 months following randomisation
Secondary outcome [20] 0 0
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)
Timepoint [20] 0 0
Measured over the 12 months following randomisation
Secondary outcome [21] 0 0
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)
Timepoint [21] 0 0
Measured over the 12 months following randomisation
Secondary outcome [22] 0 0
Pneumonia - Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)
Timepoint [22] 0 0
Measured over the 12 months following randomisation
Secondary outcome [23] 0 0
Oxygen therapy - Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
Timepoint [23] 0 0
Measured over the 12 months following randomisation
Secondary outcome [24] 0 0
Critical care admissions - Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
Timepoint [24] 0 0
Measured over the 12 months following randomisation
Secondary outcome [25] 0 0
Mechanical ventilation - Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Timepoint [25] 0 0
Measured over the 12 months following randomisation
Secondary outcome [26] 0 0
Mortality - Number of deaths (from death registry)
Timepoint [26] 0 0
Measured over the 12 months following randomisation
Secondary outcome [27] 0 0
Hospitalisation duration with fever or respiratory illness - Number of days of hospitalisation due to fever or respiratory illness (using self-reported questionnaire, medical/hospital records and/or government registries)
Timepoint [27] 0 0
Measured over the 12 months following randomisation
Secondary outcome [28] 0 0
Unplanned work absenteeism - Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
Timepoint [28] 0 0
Measured over the 12 months following randomisation
Secondary outcome [29] 0 0
Hospitalisation cost to treat COVID-19 - 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)
Timepoint [29] 0 0
Measured over the 12 months following randomisation
Secondary outcome [30] 0 0
Local and systemic adverse events to BCG vaccination in healthcare workers - Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.
Timepoint [30] 0 0
Measured over the 3 months following randomisation

Eligibility
Key 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

- 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

- Pre-randomisation blood collected
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital, Sydney - Sydney
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [3] 0 0
Sydney Children's Hospital, Randwick - Sydney
Recruitment hospital [4] 0 0
The Children's Hospital at Westmead - Sydney
Recruitment hospital [5] 0 0
Westmead Hospital - Sydney
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [8] 0 0
Royal Children's Hospital - Melbourne
Recruitment hospital [9] 0 0
Epworth Richmond - Melbourne
Recruitment hospital [10] 0 0
Monash Health- Monash Medical Centre - Melbourne
Recruitment hospital [11] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [12] 0 0
Perth Children's Hospital - Perth
Recruitment hospital [13] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
2031 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Sydney
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3052 - Melbourne
Recruitment postcode(s) [7] 0 0
3121 - Melbourne
Recruitment postcode(s) [8] 0 0
3168 - Melbourne
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
Recruitment postcode(s) [10] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Alkmaar
Country [2] 0 0
Netherlands
State/province [2] 0 0
Arnhem
Country [3] 0 0
Netherlands
State/province [3] 0 0
Breda
Country [4] 0 0
Netherlands
State/province [4] 0 0
Nieuwegein
Country [5] 0 0
Netherlands
State/province [5] 0 0
Nijmegen
Country [6] 0 0
Netherlands
State/province [6] 0 0
Utrecht
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
Bizkaia
Country [9] 0 0
Spain
State/province [9] 0 0
Santander
Country [10] 0 0
Spain
State/province [10] 0 0
Sevilla
Country [11] 0 0
Spain
State/province [11] 0 0
Zaragoza
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Exeter

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Children's Hospital
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04327206
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Prof Nigel Curtis
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Prof Nigel Curtis, MBBS PhD
Address 0 0
Country 0 0
Phone 0 0
+613 93456366
Fax 0 0
Email 0 0
nigel.curtis@rch.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04327206