Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2)

NCT04800224 | Completed Phase 2 DMC

• 1 other identifier: 31099320.6.0000.0049
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19; Inflammation

Keywords

Propolis; Covid19; Anti-Inflammatory Agents; Immunoregulation

Outcome Measures

Primary Outcomes (1)

• Length of hospital stay

  Hospitalization time after randomization (in days)

  1-28 days

Secondary Outcomes (8)

• Percentage of participants with adverse events during the use of propolis or placebo

  1-28 days

• Rate and severity of acute kidney injury during the study

  1-28 days

• Renal replacement therapy.

  1-28 days

• Rate of need for vasopressor use.

  1-28 days

• Intensive care unit (ICU) readmission

  1-28 days

Other Outcomes (1)

• Death

  1-28 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients in the Placebo group will receive an identical number of capsules containing 900 mg / day of placebo (3 capsules of 100 mg each, divided into 3 daily doses); for 10 days.

Drug: Placebo

Propolis

ACTIVE COMPARATOR

Participants in the Propolis group will receive propolis EPP-AF at a dose of 900 mg / day (3 capsules of 100 mg each, divided into 3 daily doses); for 10 days.

Drug: Standardized Brazilian Green Propolis Extract

Interventions

Standardized Brazilian Green Propolis Extract DRUG

900mg/day of Standardized Brazilian Green Propolis Extract for 10 days.

Also known as: Propolis

Propolis

Placebo DRUG

900mg/day of Placebo for 10 days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• D'Or Institute for Research and Education: lead
• Apis Flora Industrial e Comercial Ltda: collaborator

Study Sites (1)

Hospital Sao Rafael

Salvador, Estado de Bahia, 41820340, Brazil

Location

Related Publications (12)

• 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.

  PMID: 33723330 BACKGROUND

• 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.

  PMID: 31023272 BACKGROUND

• 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.

  PMID: 34311528 BACKGROUND

• 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.

  PMID: 32890967 BACKGROUND

• Maruta H, He H. PAK1-blockers: Potential Therapeutics against COVID-19. Med Drug Discov. 2020 Jun;6:100039. doi: 10.1016/j.medidd.2020.100039. Epub 2020 Apr 19.

  PMID: 32313880 BACKGROUND

• Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.

  PMID: 32142651 BACKGROUND

• Machado JL, Assuncao AK, da Silva MC, Dos Reis AS, Costa GC, Arruda Dde S, Rocha BA, Vaz MM, Paes AM, Guerra RN, Berretta AA, do Nascimento FR. Brazilian green propolis: anti-inflammatory property by an immunomodulatory activity. Evid Based Complement Alternat Med. 2012;2012:157652. doi: 10.1155/2012/157652. Epub 2012 Dec 19.

  PMID: 23320022 BACKGROUND

• 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.

  PMID: 18610553 BACKGROUND

• 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.

  PMID: 11678650 BACKGROUND

• 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.

  PMID: 22457606 BACKGROUND

• Silveira MAD, Menezes MA, de Souza SP, Galvao EBDS, Berretta AA, Caldas J, Teixeira MB, Gomes MMD, Damiani LP, Bahiense BA, Cabral JB, De Oliveira CWLM, Mascarenhas TR, Pinheiro PCG, Alves MS, de Melo RMV, Leite FM, Nonaka CKV, Souza BSF, Baptista NU, Teles F, da Guarda SF, Mendes AVA, Passos RDH. Standardized Brazilian green propolis extract (EPP-AF(R)) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial. Sci Rep. 2023 Oct 27;13(1):18405. doi: 10.1038/s41598-023-43764-w.

  PMID: 37891178 DERIVED

• 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.

  PMID: 35379306 DERIVED

MeSH Terms

Conditions

COVID-19; Inflammation

Interventions

Propolis

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Resins, Plant; Biopolymers; Polymers; Macromolecular Substances; Plant Exudates; Biological Products; Complex Mixtures

Study Officials

• Marcelo Silveira, MD, PhD

  D'Or Institute for Research and Education (IDOR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The capsules will be coated, in opaque and equal packaging, so that the researchers involved in the care of patients could not distinguish between propolis and placebo. Neither the participants, nor the principal investigator, nor the health professionals involved in the care will know which group the patients will be allocated.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A randomized, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 16, 2021
• Study Start: April 12, 2021
• Primary Completion: July 30, 2021
• Study Completion: July 30, 2021
• Last Updated: May 13, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)