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

Location

Arms

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 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.

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

Arm	Intervention/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

Arm

Intervention/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

Clinical evolution of COVID-19 [45 days of symptoms onset or diagnosis]
Classified as mild, moderate and severe
SARS-CoV-2 elimination [7 days of symptoms onset or diagnosis]
Virus detection by PCR
Seroconversion rate and titration [7 days of symptoms onset or diagnosis]
Titration of anti SARS-CoV-2 IgA, IgM and IgG

Secondary Outcome Measures

Local and systemic adverse events to BCG vaccination [3 months]
Classified according to type and severity

Other Outcome Measures

SARS-CoV-2 elimination [21 days of symptoms onset or diagnosis]
Virus detection by PCR
Seroconversion rate [21 days of symptoms onset or diagnosis]
Titration of anti SARS-CoV-2 IgA, IgM and IgG
SARS-CoV-2 elimination [45 days of symptoms onset or diagnosis]
Virus detection by PCR
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:

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)