COVID-19Phase 4BATTLENCT04369794
COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement
A Phase 4 study testing BCG in people with COVID-19 and Therapeutic Vaccine, run by University of Campinas, Brazil at 1 site in Brazil.
Trial summary
To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Therapeutic Vaccine, BCG
- What is being tested?
- BCG
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Oct 2020to 2 Aug 2023
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > 18 years of age;
- laboratory or clinical-epidemiological confirmation of COVID-19 (history of close or home contact with a laboratory-confirmed case who has fever or at least one of the respiratory signs or symptoms, in the last 14 days after contact, and for which it was not possible to carry out the specific laboratory investigation)
Who cannot join
- Immunosuppressed patients of any kind;
- Pregnant women;
- More than 14 days from the onset of symptoms;
- Not accept participation or non-signature of the IC;
- Undiagnosed cases, suspected or probable.
Trial locations and contacts
1 site in 1 country.
About this study
To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).
Read the detailed description
Prospective, randomized, double-blind, multicentre study with international design collaboration with central clinical and mechanistic outcomes with public health implications both epidemiological and therapeutic in the context of the pandemic of COVID-19, an emerging disease, which quickly disrupted health services including Brazil's Unified Health System (SUS), as well as the entire productive force and economy worldwide. Because it is recent, the basic evidence related to infection, such as incubation period, time of transmissibility, and seroconversion, is little known and the proposal's goals have the potential to redirect the vaccine. Exploring bacillus Calmette Guerin (BCG) that presents significant potential for immune activation, with recognized safety in decades of previous experience and clear potential in the context under analysis, with low cost and available, ensuring wide accessibility, especially in the context of SUS, on which it depends especially the most vulnerable portion of the Brazilian population, notably in the COVID-19 pandemic. Non-specific effects of BCG caused by monocyte epigenetic reprogramming may result in increased production of pro-inflammatory cytokines, conferring innate (trained) immunity and protection against viral infections, including SARS-CoV-2 with the potential to positively impact clinical evolution, viral elimination, and seroconversion of COVID-19 patients.
- Conditions
- COVID-19, Therapeutic Vaccine, BCG, SARS-CoV 2, Transmission
- Being tested
- BCG, Placebo
- Keywords
- BCG, Therapeutic Vaccine, COVID-19, SARS-CoV 2, Interferon Gamma, Immunoglobulin, Immunemodulation, Transmission
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCGBiological
Also called Calmette Guerin bacillus
0.1 ml of lyophilized, live and attenuated intradermal BCG vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose
PlaceboBiological
0.9% saline in the same volume as the BCG vaccine in a single dose
| Study group | Role | What they receive |
|---|---|---|
| BCG vaccine | Active comparator | BCG Group (n = 200): 0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose. Receives: Biological: BCG |
| Placebo | Placebo comparator | Placebo group (n = 200): 0.9% saline solution in the same volume as BCG vaccine in a single dose. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical evolution of COVID-19
Classified as mild, moderate and severe
Measured: 45 days of symptoms onset or diagnosis
SARS-CoV-2 elimination
Virus detection by PCR
Measured: 7 days of symptoms onset or diagnosis
Seroconversion rate and titration
Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measured: 7 days of symptoms onset or diagnosis
Secondary outcomes (1)
Local and systemic adverse events to BCG vaccination
Classified according to type and severity
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start1 Oct 2020
- Primary completion4 Jun 2022
- Study completion2 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campinas, Brazil
- Sponsor type
- University, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Paulínia Municipal Hospital
- Responsible party
- Principal investigator, Leonardo Oliveira Reis, University of Campinas, Brazil
- Investigators
- Leonardo O Reis, MD, PhD, Principal investigator, UroScience, University of Campinas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04369794
- Sponsor's protocol ID
- COVID-19 BATTLE trial
- Acronym
- BATTLE
- Status last verified
- Nov 2023
- First submitted
- 27 Apr 2020
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jalalizadeh M, Leme PAF, Buosi K, Dionato FAV, Dal Col LSB, Giacomelli CF, Reis LO. Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guerin (BCG) in the BATTLE trial. Vaccine. 2023 Oct 20;41(44):6599-6606. doi: 10.1016/j.vaccine.2023.09.031. Epub 2023 Sep 22.
PubMed 37743116Dionato FAV, Jalalizadeh M, Buosi K, Visacri MB, Dal Col LSB, Giacomelli CF, Leme PAF, Maia CL, Moriel P, Reis LO. BCG vaccine safety in COVID-19 convalescent adults: BATTLE a randomized controlled trial. Vaccine. 2022 Jul 30;40(32):4603-4608. doi: 10.1016/j.vaccine.2022.06.039. Epub 2022 Jun 20.
PubMed 35738969Jalalizadeh M, Buosi K, Dionato FAV, Dal Col LSB, Giacomelli CF, Ferrari KL, Pagliarone AC, Leme PAF, Maia CL, Yadollahvandmiandoab R, Trinh QD, Franchini KG, Bajgelman MC, Reis LO. Randomized clinical trial of BCG vaccine in patients with convalescent COVID-19: Clinical evolution, adverse events, and humoral immune response. J Intern Med. 2022 Oct;292(4):654-666. doi: 10.1111/joim.13523. Epub 2022 Jun 3.
PubMed 35599154
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement
- ClinicalTrials.gov ID
- NCT04369794
- Acronym / sponsor ID
- BATTLE / COVID-19 BATTLE trial
- Conditions
- COVID-19, Therapeutic Vaccine, BCG, SARS-CoV 2, Transmission
- Keywords
- BCG, Therapeutic Vaccine, COVID-19, SARS-CoV 2, Interferon Gamma, Immunoglobulin, Immunemodulation, Transmission
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- University of Campinas, BrazilUniversity, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Paulínia Municipal Hospital
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 4 Jun 2022 (actual)
- Study completion
- 2 Aug 2023 (actual)
- First posted
- 30 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).
Detailed description
Prospective, randomized, double-blind, multicentre study with international design collaboration with central clinical and mechanistic outcomes with public health implications both epidemiological and therapeutic in the context of the pandemic of COVID-19, an emerging disease, which quickly disrupted health services including Brazil's Unified Health System (SUS), as well as the entire productive force and economy worldwide. Because it is recent, the basic evidence related to infection, such as incubation period, time of transmissibility, and seroconversion, is little known and the proposal's goals have the potential to redirect the vaccine. Exploring bacillus Calmette Guerin (BCG) that presents significant potential for immune activation, with recognized safety in decades of previous experience and clear potential in the context under analysis, with low cost and available, ensuring wide accessibility, especially in the context of SUS, on which it depends especially the most vulnerable portion of the Brazilian population, notably in the COVID-19 pandemic. Non-specific effects of BCG caused by monocyte epigenetic reprogramming may result in increased production of pro-inflammatory cytokines, conferring innate (trained) immunity and protection against viral infections, including SARS-CoV-2 with the potential to positively impact clinical evolution, viral elimination, and seroconversion of COVID-19 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BCG vaccine | Active comparator | Biological: BCGBCG Group (n = 200): 0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose. |
| Placebo | Placebo comparator | Biological: PlaceboPlacebo group (n = 200): 0.9% saline solution in the same volume as BCG vaccine in a single dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- > 18 years of age;
- laboratory or clinical-epidemiological confirmation of COVID-19 (history of close or home contact with a laboratory-confirmed case who has fever or at least one of the respiratory signs or symptoms, in the last 14 days after contact, and for which it was not possible to carry out the specific laboratory investigation)
Key exclusion criteria (5 listed)
- Immunosuppressed patients of any kind;
- Pregnant women;
- More than 14 days from the onset of symptoms;
- Not accept participation or non-signature of the IC;
- Undiagnosed cases, suspected or probable.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCGAlso: Calmette Guerin bacillus0.1 ml of lyophilized, live and attenuated intradermal BCG vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose | Biological | BCG vaccine |
| Placebo0.9% saline in the same volume as the BCG vaccine in a single dose | Biological | Placebo |
Primary outcome
Clinical evolution of COVID-19
Time frame: 45 days of symptoms onset or diagnosis
Classified as mild, moderate and severe
SARS-CoV-2 elimination
Time frame: 7 days of symptoms onset or diagnosis
Virus detection by PCR
Seroconversion rate and titration
Time frame: 7 days of symptoms onset or diagnosis
Titration of anti SARS-CoV-2 IgA, IgM and IgG
1 secondary outcome
Local and systemic adverse events to BCG vaccination
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Derived from this study: PubMed 37743116Jalalizadeh M, Leme PAF, Buosi K, Dionato FAV, Dal Col LSB, Giacomelli CF, Reis LO. Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guerin (BCG) in the BATTLE trial. Vaccine. 2023 Oct 20;41(44):6599-6606. doi: 10.1016/j.vaccine.2023.09.031. Epub 2023 Sep 22.
- Derived from this study: PubMed 35738969Dionato FAV, Jalalizadeh M, Buosi K, Visacri MB, Dal Col LSB, Giacomelli CF, Leme PAF, Maia CL, Moriel P, Reis LO. BCG vaccine safety in COVID-19 convalescent adults: BATTLE a randomized controlled trial. Vaccine. 2022 Jul 30;40(32):4603-4608. doi: 10.1016/j.vaccine.2022.06.039. Epub 2022 Jun 20.
- Derived from this study: PubMed 35599154Jalalizadeh M, Buosi K, Dionato FAV, Dal Col LSB, Giacomelli CF, Ferrari KL, Pagliarone AC, Leme PAF, Maia CL, Yadollahvandmiandoab R, Trinh QD, Franchini KG, Bajgelman MC, Reis LO. Randomized clinical trial of BCG vaccine in patients with convalescent COVID-19: Clinical evolution, adverse events, and humoral immune response. J Intern Med. 2022 Oct;292(4):654-666. doi: 10.1111/joim.13523. Epub 2022 Jun 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leonardo O Reis, MD, PhD principal investigator
UroScience, University of Campinas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BCG in people with COVID-19 and Therapeutic Vaccine, run by University of Campinas, Brazil 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 2 inclusion and 5 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: finished, as of the sponsor's last update on 30 Nov 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical evolution of COVID-19 (time frame: 45 days of symptoms onset or diagnosis). 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 NCT04369794, which also lists 3 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 30 Nov 2023.