The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19.

Covid19 Clinical Trial

— Bee-Covid  

Official title:

The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19: a Randomized, Open and Pilot Clinical Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04480593
• Other study ID #: 31099320.6.0000.0048
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 2, 2020
• Est. completion date: August 30, 2020

Study information

• Verified date: September 2020
• Source: D'Or Institute for Research and Education
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The COVID-19 pandemic is of grave concern due its impact on human health and on the economy. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, anti-oxidant properties, and various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. This is a pilot randomized study that aims to assess the impact of using Brazilian green propolis extract against the deleterious effects of the new coronavirus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: August 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Hospitalized patients;

• Positive RT-PCR for SARS-CoV-2;

• 18 Years and older.

Exclusion Criteria:

• Pregnant women;

• People with active cancer;

• Patients undergoing transplantation of solid organs or bone marrow or who use immunosuppressive medications;

• HIV carriers;

• Allergy to propolis or any of its components;

• Bacterial infection at randomization;

• Sepsis or septic shock before randomization;

• Patients unable to use medication orally or via nasoenteral tube;

• Patients with severe chronic liver disease (Child B or C);

• Patients with advanced heart failure;

Related Conditions & MeSH terms

• Covid19

Intervention

Drug:
• Brazilian Green Propolis Extract (EPP-AF)
Green propolis extract (EPP-AF) administered orally or via nasoenteral tube.

Other:
• Standard care
Standard treatment includes, as needed, supplemental oxygen (non-invasive and invasive), antibiotics or antivirals, corticosteroids, vasopressor support, renal replacement therapy and extracorporeal membrane oxygenation (ECMO).

Locations

Country	Name	City	State
Brazil	Hospital Sao Rafael	Salvador	BA

Sponsors (2)

Lead Sponsor	Collaborator
D'Or Institute for Research and Education	Hospital Sao Rafael

Country where clinical trial is conducted

Brazil, 

References & Publications (9)

Cusinato DAC, Martinez EZ, Cintra MTC, Filgueira GCO, Berretta AA, Lanchote VL, Coelho EB. Evaluation of potential herbal-drug interactions of a standardized propolis extract (EPP-AF®) using an in vivo cocktail approach. J Ethnopharmacol. 2019 Dec 5;245:1 — 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 Inhibi — View Citation

Hori JI, Zamboni DS, Carrão DB, Goldman GH, Berretta AA. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF). Evid Based Complement Alternat Med. 2013;2013:418508. doi: 10.1155/2013/418508. Epub 2013 Apr 16. — 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 Alt — View Citation

Mani JS, Johnson JB, Steel JC, Broszczak DA, Neilsen PM, Walsh KB, Naiker M. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020 Jul 15;284:197989. doi: 10.1016/j.virusres.2020.197989. Epub 2020 Apr — View Citation

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

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 May 12;323(18):1824-1836. doi: 10.1001/jama.2020.6019. Review. — View Citation

Serkedjieva J, Manolova N, Bankova V. Anti-influenza virus effect of some propolis constituents and their analogues (esters of substituted cinnamic acids). J Nat Prod. 1992 Mar;55(3):294-302. — 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 Ne — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite clinical outcome with oxygen therapy dependency time or hospitalization time	Composite clinical outcome with oxygen therapy dependency time (in days) or hospitalization time (in days) after randomization.	1-28 days
Secondary	Percentage of participants with adverse events during the use of propolis	We will evaluate the presence or absence of symptoms related to the use of propolis through a questionnaire.	1-28 days
Secondary	Rate and severity of acute kidney injury during the study	Assess the degree of acute kidney injury according to KDIGO (through serum creatinine or urine output).	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	Need for intensive care unit (ICU)	Assess length of stay in the ICU after randomization in days	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	Variation of plasma c-reactive protein	Evaluate the variation in serum levels of c-reactive protein over the 7 days after randomization	1-7 days