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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04327206
Ethics application status
Date submitted
25/03/2020
Date registered
31/03/2020

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
Symptomatic COVID-19 by 6 months
Timepoint [1] 0 0
Measured over the 6 months following randomisation
Primary outcome [2] 0 0
Severe COVID-19 incidence over 6 months
Timepoint [2] 0 0
Measured over the 6 months following randomisation
Secondary outcome [1] 0 0
Symptomatic COVID-19 by 12 months
Timepoint [1] 0 0
Measured over the 12 months following randomisation
Secondary outcome [2] 0 0
Severe COVID-19 incidence over 12 months
Timepoint [2] 0 0
Measured over the 12 months following randomisation
Secondary outcome [3] 0 0
Time to first symptom of COVID-19
Timepoint [3] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [4] 0 0
Number of Episodes of COVID-19
Timepoint [4] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [5] 0 0
Asymptomatic SARS-CoV-2 infection
Timepoint [5] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [6] 0 0
Work absenteeism due to COVID-19
Timepoint [6] 0 0
Measured within 6 and 12 months following randomisation
Secondary outcome [7] 0 0
Bed confinement due to COVID-19
Timepoint [7] 0 0
Measured over 6 and 12 months following randomisation
Secondary outcome [8] 0 0
Symptom duration of COVID-19
Timepoint [8] 0 0
Measured over 6 and12 months following randomisation
Secondary outcome [9] 0 0
Pneumonia due to COVID-19
Timepoint [9] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [10] 0 0
Oxygen therapy due to COVID-19
Timepoint [10] 0 0
Measured over the 6 and12 months following randomisation
Secondary outcome [11] 0 0
Critical care admissions due to COVID-19
Timepoint [11] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [12] 0 0
Mechanical ventilation due to COVID-19
Timepoint [12] 0 0
Measured over the 12 months following randomisation
Secondary outcome [13] 0 0
Hospitalisation duration with COVID-19
Timepoint [13] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [14] 0 0
Mortality due to COVID-19
Timepoint [14] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [15] 0 0
Fever or respiratory illness
Timepoint [15] 0 0
Measured over the 12 months following randomisation
Secondary outcome [16] 0 0
Severe fever or respiratory illness
Timepoint [16] 0 0
Measured over the 12 months following randomisation
Secondary outcome [17] 0 0
Episodes of fever or respiratory illness
Timepoint [17] 0 0
Measured over the 12 months following randomisation
Secondary outcome [18] 0 0
Work absenteeism due to fever or respiratory illness
Timepoint [18] 0 0
Measured over the 12 months following randomisation
Secondary outcome [19] 0 0
Bed confinement due to fever or respiratory illness
Timepoint [19] 0 0
Measured over the 12 months following randomisation
Secondary outcome [20] 0 0
Symptom duration of fever or respiratory illness
Timepoint [20] 0 0
Measured over the 12 months following randomisation
Secondary outcome [21] 0 0
Pneumonia within a febrile or respiratory illness
Timepoint [21] 0 0
Measured over the 12 months following randomisation
Secondary outcome [22] 0 0
Oxygen therapy for a febrile or respiratory illness
Timepoint [22] 0 0
Measured over the 12 months following randomisation
Secondary outcome [23] 0 0
Critical care admissions for a febrile or respiratory illness
Timepoint [23] 0 0
Measured over the 12 months following randomisation
Secondary outcome [24] 0 0
Mechanical ventilation for a febrile or respiratory illness
Timepoint [24] 0 0
Measured over the 12 months following randomisation
Secondary outcome [25] 0 0
Mortality as a consequence of an episode of fever or respiratory illness
Timepoint [25] 0 0
Measured over the 12 months following randomisation
Secondary outcome [26] 0 0
Hospitalisation duration for a febrile or respiratory illness
Timepoint [26] 0 0
Measured within 6 and 12 months following randomisation
Secondary outcome [27] 0 0
Unplanned work absenteeism for an acute illness or hospitalisation
Timepoint [27] 0 0
Measured over the 6 and 12 months following randomisation
Secondary outcome [28] 0 0
Local and systemic adverse events to BCG vaccination in healthcare workers
Timepoint [28] 0 0
Measured over the 3 months following randomisation
Secondary outcome [29] 0 0
Serious Adverse Events (SAEs) to BCG vaccination in healthcare workers
Timepoint [29] 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
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
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 (=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

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
Completed
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
Brazil
State/province [1] 0 0
Amazonas
Country [2] 0 0
Brazil
State/province [2] 0 0
Mato Grosso Do Sul
Country [3] 0 0
Brazil
State/province [3] 0 0
RJ
Country [4] 0 0
Netherlands
State/province [4] 0 0
Alkmaar
Country [5] 0 0
Netherlands
State/province [5] 0 0
Arnhem
Country [6] 0 0
Netherlands
State/province [6] 0 0
Breda
Country [7] 0 0
Netherlands
State/province [7] 0 0
Nieuwegein
Country [8] 0 0
Netherlands
State/province [8] 0 0
Nijmegen
Country [9] 0 0
Netherlands
State/province [9] 0 0
Utrecht
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Bizkaia
Country [12] 0 0
Spain
State/province [12] 0 0
Santander
Country [13] 0 0
Spain
State/province [13] 0 0
Sevilla
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Devon
Country [15] 0 0
United Kingdom
State/province [15] 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
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Bill and Melinda Gates Foundation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.