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

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ClinicalTrials.gov Identifier: NCT04369794
Recruitment Status : Recruiting
First Posted : April 30, 2020
Last Update Posted : August 7, 2020
Sponsor:
Collaborators:
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Instituto de Infectologia Emílio Ribas
Pontifícia Universidade Católica de Campinas, PUC-Campinas
Faculty of Medicine of Ribeirão Preto (FMRP-USP)
Faculdade de Medicina de Botucatu, UNESP, Botucatu, Brasil
Federal University of São Paulo
State Hospital Dr. Leandro Franceschini, Sumaré, Unicamp
Paulinia Municipal Hospital
Information provided by (Responsible Party):
Leonardo Oliveira Reis, University of Campinas, Brazil

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 disease Intervention/treatment Phase
COVID-19 Therapeutic Vaccine BCG SARS-CoV 2 Transmission 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 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
Estimated Study Start Date : August 10, 2020
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: BCG vaccine
BCG Group (n = 500): 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 Name: Calmette Guerin bacillus

Placebo Comparator: Placebo
Placebo group (n = 500): 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




Primary Outcome Measures :
  1. Clinical evolution of COVID-19 [ Time Frame: 45 days of symptoms onset or diagnosis ]
    Classified as mild, moderate and severe

  2. SARS-CoV-2 elimination [ Time Frame: 7 days of symptoms onset or diagnosis ]
    Virus detection by PCR

  3. Seroconversion rate and titration [ Time Frame: 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 [ Time Frame: 3 months ]
    Classified according to type and severity


Other Outcome Measures:
  1. SARS-CoV-2 elimination [ Time Frame: 21 days of symptoms onset or diagnosis ]
    Virus detection by PCR

  2. Seroconversion rate [ Time Frame: 21 days of symptoms onset or diagnosis ]
    Titration of anti SARS-CoV-2 IgA, IgM and IgG

  3. SARS-CoV-2 elimination [ Time Frame: 45 days of symptoms onset or diagnosis ]
    Virus detection by PCR

  4. Seroconversion rate and titration [ Time Frame: 45 days of symptoms onset or diagnosis ]
    Titration of anti SARS-CoV-2 IgA, IgM and IgG



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369794


Contacts
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Contact: Karen L Ferrari, PhD +55 19 3521 7481 karenferrari@gmail.com

Locations
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Brazil
Hospital das Clínicas Unicamp Recruiting
Campinas, SP, Brazil, 13083-887
Contact: Karen L Ferrari, PhD    +551935217116    karenferrari@gmail.com   
Principal Investigator: Leonardo O Reis, MD, MSc, PhD         
Sponsors and Collaborators
University of Campinas, Brazil
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Instituto de Infectologia Emílio Ribas
Pontifícia Universidade Católica de Campinas, PUC-Campinas
Faculty of Medicine of Ribeirão Preto (FMRP-USP)
Faculdade de Medicina de Botucatu, UNESP, Botucatu, Brasil
Federal University of São Paulo
State Hospital Dr. Leandro Franceschini, Sumaré, Unicamp
Paulinia Municipal Hospital
Investigators
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Principal Investigator: Leonardo O Reis, MD, PhD UroScience, University of Campinas
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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: April 30, 2020    Key Record Dates
Last Update Posted: August 7, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, University of Campinas, Brazil:
BCG
Therapeutic Vaccine
COVID-19
SARS-CoV 2
Interferon Gamma
Immunoglobulin
Immunemodulation
Transmission
Additional relevant MeSH terms:
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BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs