Clinical trial NCT04369794: COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement
Official title: COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Therapeutic Vaccine
BCG
SARS-CoV 2
Transmission
Keywords: BCG
Therapeutic Vaccine
COVID-19
SARS-CoV 2
Interferon Gamma
Immunoglobulin
Immunemodulation
Transmission
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
name: Paulínia Municipal Hospital
First posted: 2020-04-30
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Clinical evolution of COVID-19
timeFrame: 45 days of symptoms onset or diagnosis
measure: SARS-CoV-2 elimination
timeFrame: 7 days of symptoms onset or diagnosis
measure: Seroconversion rate and titration
timeFrame: 7 days of symptoms onset or diagnosis
Secondary outcomes:
measure: Local and systemic adverse events to BCG vaccination
timeFrame: 3 months
Other outcomes:
measure: SARS-CoV-2 elimination
timeFrame: 21 days of symptoms onset or diagnosis
measure: Seroconversion rate
timeFrame: 21 days of symptoms onset or diagnosis
measure: SARS-CoV-2 elimination
timeFrame: 45 days of symptoms onset or diagnosis
measure: Seroconversion rate and titration
timeFrame: 45 days of symptoms onset or diagnosis
Locations:
city: Campinas
country: Brazil
facility: Hospital das Clínicas Unicamp
state: SP
Study officials:
affiliation: UroScience, University of Campinas
name: Leonardo O Reis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dionato 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.
citation: Jalalizadeh 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.