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

Murdoch Childrens Research Institute

Status and phase: Completed; Phase 3

Conditions: COVID-19; Corona Virus Infection; Coronavirus Disease 2019 (COVID-19); Respiratory Illness

Treatments: Drug: BCG Vaccine; Drug: 0.9%NaCl

Study type: Interventional

Funder types: Other

Identifiers

NCT04327206

62586

INV-017302 (Other Grant/Funding Number)

U1111-1256-4104 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6,828 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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6,828 participants in 2 patient groups, including a placebo group

BCG vaccine

Experimental group

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).

Treatment:

Drug: BCG Vaccine

0.9% Saline

Placebo Comparator group

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).

Treatment:

Drug: 0.9%NaCl