Clinical trial NCT04800224: Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2)
Official title: The Use of the Standardized Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients: A Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Inflammation
Keywords: Propolis
Covid19
Anti-Inflammatory Agents
Immunoregulation
Lead sponsor: D'Or Institute for Research and Education
Sponsor class: OTHER
Collaborators: name: Apis Flora Industrial e Comercial Ltda
First posted: 2021-03-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Among candidate adjunct treatment options, propolis, produced by honey bees from bioactive plant exudates, has shown potential against viral targets and has demonstrated immunoregulatory properties.

Detailed description: To evaluate the efficacy and safety of oral propolis as an adjunct treatment for SARS-CoV-2 infection, we designed a randomized, double-blind, placebo-controlled trial (Bee-Covid2) (The Use of Brazilian Green Propolis Extract (EPP-AF®) in Patients Affected by COVID-19).

Eligibility criteria: Inclusion Criteria:

* Older than 18 years;
* Diagnosis of coronavirus infection confirmed by polymerase chain reaction - reverse transcriptase testing;
* Symptoms started within 14 days of the randomization date

Exclusion Criteria:

* Pregnant or lactating women;
* Known hypersensitivity to propolis;
* Propolis use less than 30 days from the randomization date;
* Active cancer;
* Human immunodeficiency virus carriers;
* Patients undergoing transplantation of solid organs or bone marrow or who were using immunosuppressive medications;
* Bacterial infection at randomization, sepsis or septic shock related to bacterial infection at randomization;
* Impossibility of using the medication orally or by nasoenteral tube;
* Known hepatic failure or advanced heart failure (New York Heart Association \[NYHA\] class III or IV).
* End Stage Renal Disease (ESRD).

Primary outcomes:
measure: Length of hospital stay
timeFrame: 1-28 days
Secondary outcomes:
measure: Percentage of participants with adverse events during the use of propolis or placebo
timeFrame: 1-28 days
measure: Rate and severity of acute kidney injury during the study
timeFrame: 1-28 days
measure: Renal replacement therapy.
timeFrame: 1-28 days
measure: Rate of need for vasopressor use.
timeFrame: 1-28 days
measure: Intensive care unit (ICU) readmission
timeFrame: 1-28 days
measure: Invasive oxygenation time
timeFrame: 1-28 days
measure: Need for Intra-Aortic Balloon Pump
timeFrame: 1-28 days
measure: Need for Extracorporeal Oxygenation Membrane (ECMO)
timeFrame: 1-28 days
Other outcomes:
measure: Death
timeFrame: 1-28 days
Locations:
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
state: BA
Study officials:
affiliation: D'Or Institute for Research and Education (IDOR)
name: Marcelo Silveira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Silveira MAD, Capcha JMC, Sanches TR, de Sousa Moreira R, Garnica MS, Shimizu MH, Berretta A, Teles F, Noronha IL, Andrade L. Green propolis extract attenuates acute kidney injury and lung injury in a rat model of sepsis. Sci Rep. 2021 Mar 15;11(1):5925. doi: 10.1038/s41598-021-85124-6.
citation: Silveira MAD, Teles F, Berretta AA, Sanches TR, Rodrigues CE, Seguro AC, Andrade L. Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled trial. BMC Nephrol. 2019 Apr 25;20(1):140. doi: 10.1186/s12882-019-1337-7.
citation: Silveira MAD, De Jong D, Berretta AA, Galvao EBDS, Ribeiro JC, Cerqueira-Silva T, Amorim TC, Conceicao LFMRD, Gomes MMD, Teixeira MB, Souza SP, Santos MHCAD, San Martin RLA, Silva MO, Lirio M, Moreno L, Sampaio JCM, Mendonca R, Ultchak SS, Amorim FS, Ramos JGR, Batista PBP, Guarda SNFD, Mendes AVA, Passos RDH; BeeCovid Team. Efficacy of Brazilian green propolis (EPP-AF(R)) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial. Biomed Pharmacother. 2021 Jun;138:111526. doi: 10.1016/j.biopha.2021.111526. Epub 2021 Mar 20.
citation: Berretta AA, Silveira MAD, Condor Capcha JM, De Jong D. Propolis and its potential against SARS-CoV-2 infection mechanisms and COVID-19 disease: Running title: Propolis against SARS-CoV-2 infection and COVID-19. Biomed Pharmacother. 2020 Nov;131:110622. doi: 10.1016/j.biopha.2020.110622. Epub 2020 Aug 17.
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citation: Shimizu T, Hino A, Tsutsumi A, Park YK, Watanabe W, Kurokawa M. Anti-influenza virus activity of propolis in vitro and its efficacy against influenza infection in mice. Antivir Chem Chemother. 2008;19(1):7-13. doi: 10.1177/095632020801900102.
citation: Ito J, Chang FR, Wang HK, Park YK, Ikegaki M, Kilgore N, Lee KH. Anti-AIDS agents. 48.(1) Anti-HIV activity of moronic acid derivatives and the new melliferone-related triterpenoid isolated from Brazilian propolis. J Nat Prod. 2001 Oct;64(10):1278-81. doi: 10.1021/np010211x.
citation: Berretta AA, Nascimento AP, Bueno PC, Vaz MM, Marchetti JM. Propolis standardized extract (EPP-AF(R)), an innovative chemically and biologically reproducible pharmaceutical compound for treating wounds. Int J Biol Sci. 2012;8(4):512-21. doi: 10.7150/ijbs.3641. Epub 2012 Mar 21.
citation: Silveira MAD, de Souza SP, Dos Santos Galvao EB, Teixeira MB, Gomes MMD, Damiani LP, Bahiense BA, Cabral JB, De Oliveira CWLM, Mascarenhas TR, Pinheiro PCG, Alves MS, de Melo RMV, Berretta AA, Leite FM, Nonaka CKV, de Freitas Souza BS, Mendes AVA, da Guarda SF, da Hora Passos R. 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. Trials. 2022 Apr 4;23(1):255. doi: 10.1186/s13063-022-06176-1.