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

Covid19 Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04800224
• Other study ID #: 31099320.6.0000.0049
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 12, 2021
• Est. completion date: July 30, 2021

Study information

• Verified date: May 2022
• Source: D'Or Institute for Research and Education
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: July 30, 2021
• Est. primary completion date: July 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Inflammation

Intervention

Drug:
• Standardized Brazilian Green Propolis Extract
900mg/day of Standardized Brazilian Green Propolis Extract for 10 days.
• Placebo
900mg/day of Placebo for 10 days.

Locations

Country	Name	City	State
Brazil	Hospital Sao Rafael	Salvador	BA

Sponsors (2)

Lead Sponsor	Collaborator
D'Or Institute for Research and Education	Apis Flora Industrial e Comercial Ltda

Country where clinical trial is conducted

Brazil, 

References & Publications (10)

Berretta AA, Nascimento AP, Bueno PC, Vaz MM, Marchetti JM. Propolis standardized extract (EPP-AF®), 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. — View Citation

Berretta AA, Silveira MAD, Cóndor 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. Review. — View Citation

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann 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. — View 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. — View Citation

Machado JL, Assunção 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. — View Citation

MAD Silveira, D De Jong, AA Berretta, et.al. Efficacy of propolis as an adjunct treatment for hospitalized COVID-19 patients: a randomized, controlled clinical trial. MedRxiv preprint doi: https://doi.org/10.1101/2021.01.08.20248932.

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. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Death	Assess mortality rate	1-28 days
Primary	Length of hospital stay	Hospitalization time after randomization (in days)	1-28 days
Secondary	Percentage of participants with adverse events during the use of propolis or placebo	We will evaluate the presence or absence of symptoms related to the use of propolis or placebo.	1-28 days
Secondary	Rate and severity of acute kidney injury during the study	Assess the degree of acute kidney injury according to KDIGO.	1-28 days
Secondary	Renal replacement therapy.	Assess need or not for renal replacement therapy	1-28 days
Secondary	Rate of need for vasopressor use.	Describe the time needed for vasopressors in days after randomization.	1-28 days
Secondary	Intensive care unit (ICU) readmission	Rate of readmission to the ICU after randomization	1-28 days
Secondary	Invasive oxygenation time	Assess the need for mechanical ventilation in days after randomization.	1-28 days
Secondary	Need for Intra-Aortic Balloon Pump	Assess the need for Intra-Aortic Balloon Pump in days after randomization.	1-28 days
Secondary	Need for Extracorporeal Oxygenation Membrane (ECMO)	Assess the need for Extracorporeal Oxygenation Membrane in days after randomization.	1-28 days