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COVID 19 VaccinePhase 2ProBCGNCT04659941

Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers

A Phase 2 study testing BCG vaccine and 0.9% sodium chloride (NaCl) saline solution in people with COVID 19 Vaccine, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The disease promoted by coronavirus (COVID-19) is caused by Severe Acute Respiratory Syndrome (SARS) caused by Coronavirus type 2 (CoV2), being the first cases identified in December 2019 in China after exposure to the animal market in Wuhan city, China. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
COVID 19 Vaccine
What is being tested?
BCG vaccine and 0.9% sodium chloride (NaCl) saline solution
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
752 participants
Where
1 siteBrazil
Study dates
1 Oct 2020to 1 Apr 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Individuals aged 18 ≥, male or female, not infected with SARS-CoV-2
  • Agreement to participate in the study by signing the Free Informed Consent (FIC)
  • Not being pregnant (in case of women able to become pregnant)
  • Have not received a specific vaccine against COVID-19 or, if vaccinated against SARS-CoV-2, have received the complete immunization schedule only with vaccines approved by ANVISA and implemented by the National Immunization Program, (including the second dose) within a minimum of 15 days prior to the date of inclusion in the study
  • If the participant have not received a specific vaccine against COVID-19 approved by ANVISA, be aware and agree to be able to receive them only 15 days after the intervention proposed in this study

Who cannot join

  • Professionals with a history of SARS-CoV-2 confirmed infection through RT-PCR or who have already presented clinical and molecular diagnosis of COVID-19 prior to the study
  • Individuals who have not underwent confirmatory tests for COVID-19
  • Breastfeeding
  • Individuals with primary or acquired immunodeficiency
  • Individuals affected by malignant neoplasms
  • Patients treated with high-dose corticosteroids (equivalent to the prednisone dose of 20 mg/day or more) for more than two weeks
Show all 18Show fewer
  • Patients using other immunosuppressive therapies (antineoplastic chemotherapy, radiotherapy, among others)
  • Individuals with autoimmune diseases
  • Dermatological conditions at the vaccine site or generalized
  • Individuals under treatment for active tuberculosis
  • Individuals with a history of previous tuberculosis treatment
  • Individuals with febrile symptoms [body temperature ≥ 37.5 celsius degree (ºC) in the last 48h]
  • Participation in other prevention clinical trials for COVID-19 (vaccines already approved by ANVISA for use by the National Immunization Program are not included in this item)
  • Report of vaccination with live microorganism administered in the month prior to randomization
  • Require that, if another vaccination with live microorganism is required, it is administered in the month following randomisation (If the other live vaccine can be administered on the same day, this exclusion criterion does not apply)
  • Known anaphylactic reaction to any ingredient in BCG vaccine
  • Adverse reaction prior to BCG vaccine [significant local reaction (abscess) or suppurative lymphadenitis]
  • BCG vaccine administered in the last year

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Universidade Federal do Rio de Janeiro

    Rio de Janeiro, Rio de Janeiro, 21941-590

Other trials in Brazil

About this study

The disease promoted by coronavirus (COVID-19) is caused by Severe Acute Respiratory Syndrome (SARS) caused by Coronavirus type 2 (CoV2), being the first cases identified in December 2019 in China after exposure to the animal market in Wuhan city, China. From the first case to the present day, the COVID-19 epidemic has been identified in 185 countries, with the notification of 2,666,154 cases and 186,144 deaths. In Brazil, more than 45,757 cases and 2,906 confirmed deaths by COVID-19 have been confirmed (Visualized on Apr 23 2020). In our country, to date, testing for COVID-19 occurs only in severe cases and few centers offer the service to health care workers, a population at high risk of infection. BCG is a vaccine produced from a live attenuated strain derived from a Mycobacterium bovis isolate and is widely used worldwide as a tuberculosis (TB) vaccine, but there are studies demonstrating non-specific immunotherapeutic mechanisms of this vaccine that signal a possible relationship with the lowest morbidity and mortality associated with COVID-19 infections worldwide. The present study aims to analyze the role of BCG in the prevention of SARS-CoV-2 infection and also in the occurrence of severe forms of COVID-19 in addition to evaluating the immune response mediated by this vaccine in voluntary health care workers.

Read the detailed description

Study detailed description can be seen on the protocol attached.

Being tested
BCG vaccine, 0.9% sodium chloride (NaCl) saline solution
Keywords
COVID 19, BCG vaccine
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BCG vaccineBiological

    Using aseptic methods, 1 mL of Sterile Water for Injection, is added to one vial of vaccine. Gently swirl the vial until a homogenous suspension is obtained. Avoid forceful agitation which may cause clumping of the mycobacteria. Drop the immunizing dose of 0.1 mL of BCG VACCINE from the syringe and needle onto the cleansed surface of the skin.

  • 0.9% sodium chloride (NaCl) saline solutionBiological

    A 0.1 ml of 0.9% NaCl saline solution applied intradermally in the lower insertion of the deltoid muscle of the right arm will be used as placebo, except contraindications or impossibilities.

Study groups in NCT04659941
Study groupRoleWhat they receive
BCG vaccineExperimental0.1 ml of the reconstituted vaccine to be administered intradermally in the lower insertion of the deltoid muscle, preferably on the right side, in only one occasion
Receives: Biological: BCG vaccine
0.9% sodium chloride (NaCl) saline solutionPlacebo comparator0.1 ml of 0.9% NaCl saline solution to be administered intradermally in the lower insertion of the deltoid muscle, preferably on the right side, in only one occasion
Receives: Biological: 0.9% sodium chloride (NaCl) saline solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Compare the cumulative incidence of SARS-CoV-2 infection

    It is estimated that it will take 376 individuals in each of the comparison groups to ensure a statistical power of 85% for the detection of a risk difference of 5%, considering that the 6 months of follow-up, for a type I error of 5%.

    Measured: 6 months

  2. Compare the cumulative incidence of severe forms of COVID-19

    With 376 individuals in each of the comparison groups the study will have a statistical power of approximately 75% for the detection of a risk difference of 2%, considering that the control group will have an accumulated incidence of more severe forms of COVID-19 of 2.5% after 6 months of follow-up, for a type I error of 5%.

    Measured: 6 months

  3. Assess the BCG vaccine-mediated immune response in health care workers

    SARS-CoV2 infection is estimated to occur in approximately 10% of BCG-vaccinated healthcare professionals (experimental group) and in 30% of non-BCG-vaccinated healthcare professionals (placebo group) In this scenario, with the bearing of 372 health professionals in each arm, SARS-CoV2 infection is expected to be detected in 50 BCG-vaccinated professionals and 150 professionals not vaccinated with BCG. For each subgroup (vaccinated and not vaccinated with BCG) it will be possible to identify the predictive biomarkers of infection by comparing infected professionals with those who were not infected with SARS-CoV2.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2020
  2. Study start1 Oct 2020
  3. Primary completion1 Oct 2022
  4. Study completion1 Apr 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
752 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04659941
Sponsor's protocol ID
31942220.8.1001.5257
Acronym
ProBCG
Status last verified
May 2023
First submitted
8 Dec 2020
Last updated
11 May 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, Stensballe L, Diness BR, Lausch KR, Lund N, Biering-Sorensen S, Whittle H, Benn CS. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis. 2011 Jul 15;204(2):245-52. doi: 10.1093/infdis/jir240.

    PubMed 21673035

  • Goodridge HS, Ahmed SS, Curtis N, Kollmann TR, Levy O, Netea MG, Pollard AJ, van Crevel R, Wilson CB. Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol. 2016 Jun;16(6):392-400. doi: 10.1038/nri.2016.43. Epub 2016 May 9.

    PubMed 27157064

  • Kleinnijenhuis J, Quintin J, Preijers F, Benn CS, Joosten LA, Jacobs C, van Loenhout J, Xavier RJ, Aaby P, van der Meer JW, van Crevel R, Netea MG. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun. 2014;6(2):152-8. doi: 10.1159/000355628. Epub 2013 Oct 30.

    PubMed 24192057

  • Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ. Trained immunity: A program of innate immune memory in health and disease. Science. 2016 Apr 22;352(6284):aaf1098. doi: 10.1126/science.aaf1098. Epub 2016 Apr 21.

    PubMed 27102489

  • Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res. 2014 Aug;59(1-3):118-28. doi: 10.1007/s12026-014-8534-z.

    PubMed 24845462

  • Netea MG, Giamarellos-Bourboulis EJ, Dominguez-Andres J, Curtis N, van Crevel R, van de Veerdonk FL, Bonten M. Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection. Cell. 2020 May 28;181(5):969-977. doi: 10.1016/j.cell.2020.04.042. Epub 2020 May 4.

    PubMed 32437659

  • Ozdemir C, Kucuksezer UC, Tamay ZU. Is BCG vaccination affecting the spread and severity of COVID-19? Allergy. 2020 Jul;75(7):1824-1827. doi: 10.1111/all.14344. Epub 2020 May 12. No abstract available.

    PubMed 32330314

  • Urashima M, Otani K, Hasegawa Y, Akutsu T. BCG Vaccination and Mortality of COVID-19 across 173 Countries: An Ecological Study. Int J Environ Res Public Health. 2020 Aug 3;17(15):5589. doi: 10.3390/ijerph17155589.

    PubMed 32756371

  • Santos AP, Werneck GL, Dalvi APR, Dos Santos CC, Tierno PFGMM, Condelo HS, Macedo B, de Medeiros Leung JA, de Souza Nogueira J, Malvao L, Galliez R, Aguiar R, Stefan R, Knackfuss SM, da Silva EC, Castineiras TMPP, de Andrade Medronho R, E Silva JRL, Alves RLR, de Moraes Sobrino Porto LC, Rodrigues LS, Kritski AL, de Queiroz Mello FC. The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2-The results of ProBCG: a multicenter randomized clinical trial in Brazil. Int J Infect Dis. 2023 May;130:8-16. doi: 10.1016/j.ijid.2023.02.014. Epub 2023 Feb 24.

    PubMed 36841502

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BCG vaccine and 0.9% sodium chloride (NaCl) saline solution in people with COVID 19 Vaccine, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 11 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Compare the cumulative incidence of SARS-CoV-2 infection (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04659941, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2023.

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