The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial

Marcelo Augusto Duarte Silveira, Sergio Pinto de Souza, Erica Batista Dos Santos Galvão, Maurício Brito Teixeira, Marcel Miranda Dantas Gomes, Lucas Petri Damiani, Bruno Andrade Bahiense, Julia Barros Cabral, Cicero Wandson Luiz Macedo De Oliveira, Talita Rocha Mascarenhas, Priscila Carvalho Guedes Pinheiro, Milena Souza Alves, Rodrigo Morel Vieira de Melo, Andresa Aparecida Berretta, Flávia Mendes Leite, Carolina Kymie Vasques Nonaka, Bruno Solano de Freitas Souza, Ana Verena Almeida Mendes, Suzete Farias da Guarda, Rogério da Hora Passos, Marcelo Augusto Duarte Silveira, Sergio Pinto de Souza, Erica Batista Dos Santos Galvão, Maurício Brito Teixeira, Marcel Miranda Dantas Gomes, Lucas Petri Damiani, Bruno Andrade Bahiense, Julia Barros Cabral, Cicero Wandson Luiz Macedo De Oliveira, Talita Rocha Mascarenhas, Priscila Carvalho Guedes Pinheiro, Milena Souza Alves, Rodrigo Morel Vieira de Melo, Andresa Aparecida Berretta, Flávia Mendes Leite, Carolina Kymie Vasques Nonaka, Bruno Solano de Freitas Souza, Ana Verena Almeida Mendes, Suzete Farias da Guarda, Rogério da Hora Passos

Abstract

Background: The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay.

Methods: BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO).

Discussion: This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19.

Trial registration: ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.

Keywords: ACE2; Anti-inflammatory agents; COVID-19; Immunoregulation; PAK1 blocker; Propolis; Protocol; Randomized controlled trial; TMPRSS2.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

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