The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19. (Bee-Covid)
Primary Purpose
Covid19
Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Brazilian Green Propolis Extract (EPP-AF)
Standard care
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring Propolis, Covid19, SARS-CoV-2, Anti-inflammatory
Eligibility Criteria
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;
Sites / Locations
- Hospital Sao Rafael
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Control
EPP-AF 400mg/day
EPP-AF 800mg/day
Arm Description
standard care.
Green propolis extract (EPP-AF) at a dose of 400mg / day in addition to the standard treatment.
Green propolis extract (EPP-AF) at a dose of 800mg / day in addition to the standard treatment.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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).
Renal replacement therapy.
Assess need or not for renal replacement therapy.
Rate of need for vasopressor use
Describe the time needed for vasopressors in days after randomization
Need for intensive care unit (ICU)
Assess length of stay in the ICU after randomization in days
Intensive care unit (ICU) readmission
Rate of readmission to the ICU after randomization
Invasive oxygenation time
Assess the need for mechanical ventilation in days after randomization.
Variation of plasma c-reactive protein
Evaluate the variation in serum levels of c-reactive protein over the 7 days after randomization
Full Information
NCT ID
NCT04480593
First Posted
July 12, 2020
Last Updated
September 28, 2020
Sponsor
D'Or Institute for Research and Education
Collaborators
Hospital Sao Rafael
1. Study Identification
Unique Protocol Identification Number
NCT04480593
Brief Title
The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19.
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
June 2, 2020 (Actual)
Primary Completion Date
August 30, 2020 (Actual)
Study Completion Date
August 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
D'Or Institute for Research and Education
Collaborators
Hospital Sao Rafael
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
Propolis, Covid19, SARS-CoV-2, Anti-inflammatory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
three parallel groups randomly assigned
Masking
Outcomes Assessor
Masking Description
The individual who evaluates the results of interest to the study will not have access to the study steps before the analysis.
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Active Comparator
Arm Description
standard care.
Arm Title
EPP-AF 400mg/day
Arm Type
Experimental
Arm Description
Green propolis extract (EPP-AF) at a dose of 400mg / day in addition to the standard treatment.
Arm Title
EPP-AF 800mg/day
Arm Type
Experimental
Arm Description
Green propolis extract (EPP-AF) at a dose of 800mg / day in addition to the standard treatment.
Intervention Type
Drug
Intervention Name(s)
Brazilian Green Propolis Extract (EPP-AF)
Other Intervention Name(s)
Standard care
Intervention Description
Green propolis extract (EPP-AF) administered orally or via nasoenteral tube.
Intervention Type
Other
Intervention Name(s)
Standard care
Intervention Description
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).
Primary Outcome Measure Information:
Title
Composite clinical outcome with oxygen therapy dependency time or hospitalization time
Description
Composite clinical outcome with oxygen therapy dependency time (in days) or hospitalization time (in days) after randomization.
Time Frame
1-28 days
Secondary Outcome Measure Information:
Title
Percentage of participants with adverse events during the use of propolis
Description
We will evaluate the presence or absence of symptoms related to the use of propolis through a questionnaire.
Time Frame
1-28 days
Title
Rate and severity of acute kidney injury during the study
Description
Assess the degree of acute kidney injury according to KDIGO (through serum creatinine or urine output).
Time Frame
1-28 days
Title
Renal replacement therapy.
Description
Assess need or not for renal replacement therapy.
Time Frame
1-28 days
Title
Rate of need for vasopressor use
Description
Describe the time needed for vasopressors in days after randomization
Time Frame
1-28 days
Title
Need for intensive care unit (ICU)
Description
Assess length of stay in the ICU after randomization in days
Time Frame
1-28 days
Title
Intensive care unit (ICU) readmission
Description
Rate of readmission to the ICU after randomization
Time Frame
1-28 days
Title
Invasive oxygenation time
Description
Assess the need for mechanical ventilation in days after randomization.
Time Frame
1-28 days
Title
Variation of plasma c-reactive protein
Description
Evaluate the variation in serum levels of c-reactive protein over the 7 days after randomization
Time Frame
1-7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcelo Silveira, MD, PhD
Organizational Affiliation
D'Or Institute for Research and Education (IDOR)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Sao Rafael
City
Salvador
State/Province
BA
ZIP/Postal Code
41820340
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23690844
Citation
Hori JI, Zamboni DS, Carrao 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.
Results Reference
background
PubMed Identifier
32282022
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.
Results Reference
result
PubMed Identifier
32313880
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.
Results Reference
result
PubMed Identifier
1593279
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. doi: 10.1021/np50081a003.
Results Reference
result
PubMed Identifier
32142651
Citation
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.
Results Reference
result
PubMed Identifier
23320022
Citation
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.
Results Reference
result
PubMed Identifier
32360300
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 30.
Results Reference
result
PubMed Identifier
31023272
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.
Results Reference
result
PubMed Identifier
31442620
Citation
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(R)) using an in vivo cocktail approach. J Ethnopharmacol. 2019 Dec 5;245:112174. doi: 10.1016/j.jep.2019.112174. Epub 2019 Aug 20.
Results Reference
result
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The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19.
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