BATTLE: COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement

Sponsor
University of Campinas, Brazil (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04369794
Collaborator
Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other), Pontifícia Universidade Católica de Campinas, PUC-Campinas (Other), State Hospital Dr. Leandro Franceschini, Sumaré, Unicamp (Other), Paulínia Municipal Hospital (Other)
400
Enrollment
1
Location
2
Arms
34
Anticipated Duration (Months)
11.8
Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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).

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: BCG
  • Biological: Placebo
Phase 4

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

Study Type:
Interventional
Actual Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement
Actual Study Start Date :
Oct 1, 2020
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: BCG vaccine

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.

Biological: BCG
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
Other Names:
  • Calmette Guerin bacillus
  • Placebo Comparator: Placebo

    Placebo group (n = 200): 0.9% saline solution in the same volume as BCG vaccine in a single dose.

    Biological: Placebo
    0.9% saline in the same volume as the BCG vaccine in a single dose

    Outcome Measures

    Primary Outcome Measures

    1. Clinical evolution of COVID-19 [45 days of symptoms onset or diagnosis]

      Classified as mild, moderate and severe

    2. SARS-CoV-2 elimination [7 days of symptoms onset or diagnosis]

      Virus detection by PCR

    3. Seroconversion rate and titration [7 days of symptoms onset or diagnosis]

      Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Secondary Outcome Measures

    1. Local and systemic adverse events to BCG vaccination [3 months]

      Classified according to type and severity

    Other Outcome Measures

    1. SARS-CoV-2 elimination [21 days of symptoms onset or diagnosis]

      Virus detection by PCR

    2. Seroconversion rate [21 days of symptoms onset or diagnosis]

      Titration of anti SARS-CoV-2 IgA, IgM and IgG

    3. SARS-CoV-2 elimination [45 days of symptoms onset or diagnosis]

      Virus detection by PCR

    4. Seroconversion rate and titration [45 days of symptoms onset or diagnosis]

      Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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)

    Exclusion Criteria:
    • 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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Hospital das Clínicas UnicampCampinasSPBrazil13083-887

    Sponsors and Collaborators

    • University of Campinas, Brazil
    • Conselho Nacional de Desenvolvimento Científico e Tecnológico
    • Pontifícia Universidade Católica de Campinas, PUC-Campinas
    • State Hospital Dr. Leandro Franceschini, Sumaré, Unicamp
    • Paulínia Municipal Hospital

    Investigators

    • Principal Investigator: Leonardo O Reis, MD, PhD, UroScience, University of Campinas

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Leonardo Oliveira Reis, Professor Livre Docente, University of Campinas, Brazil
    ClinicalTrials.gov Identifier:
    NCT04369794
    Other Study ID Numbers:
    • COVID-19 BATTLE trial
    First Posted:
    Apr 30, 2020
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Leonardo Oliveira Reis, Professor Livre Docente, University of Campinas, Brazil
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 4, 2022