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

Primary Purpose

Covid19, Inflammation

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Standardized Brazilian Green Propolis Extract
Placebo
Sponsored by
D'Or Institute for Research and Education
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring Propolis, Covid19, Anti-Inflammatory Agents, Immunoregulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Hospital Sao Rafael

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Propolis

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Length of hospital stay
Hospitalization time after randomization (in days)

Secondary Outcome Measures

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.
Rate and severity of acute kidney injury during the study
Assess the degree of acute kidney injury according to KDIGO.
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.
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.
Need for Intra-Aortic Balloon Pump
Assess the need for Intra-Aortic Balloon Pump in days after randomization.
Need for Extracorporeal Oxygenation Membrane (ECMO)
Assess the need for Extracorporeal Oxygenation Membrane in days after randomization.

Full Information

First Posted
March 12, 2021
Last Updated
May 11, 2022
Sponsor
D'Or Institute for Research and Education
Collaborators
Apis Flora Industrial e Comercial Ltda
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1. Study Identification

Unique Protocol Identification Number
NCT04800224
Brief Title
Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2)
Acronym
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

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
April 12, 2021 (Actual)
Primary Completion Date
July 30, 2021 (Actual)
Study Completion Date
July 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
D'Or Institute for Research and Education
Collaborators
Apis Flora Industrial e Comercial Ltda

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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Inflammation
Keywords
Propolis, Covid19, Anti-Inflammatory Agents, Immunoregulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
A randomized, double-blind, placebo-controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Propolis
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Standardized Brazilian Green Propolis Extract
Other Intervention Name(s)
Propolis
Intervention Description
900mg/day of Standardized Brazilian Green Propolis Extract for 10 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
900mg/day of Placebo for 10 days.
Primary Outcome Measure Information:
Title
Length of hospital stay
Description
Hospitalization time after randomization (in days)
Time Frame
1-28 days
Secondary Outcome Measure Information:
Title
Percentage of participants with adverse events during the use of propolis or placebo
Description
We will evaluate the presence or absence of symptoms related to the use of propolis or placebo.
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.
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
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
Need for Intra-Aortic Balloon Pump
Description
Assess the need for Intra-Aortic Balloon Pump in days after randomization.
Time Frame
1-28 days
Title
Need for Extracorporeal Oxygenation Membrane (ECMO)
Description
Assess the need for Extracorporeal Oxygenation Membrane in days after randomization.
Time Frame
1-28 days
Other Pre-specified Outcome Measures:
Title
Death
Description
Assess mortality rate
Time Frame
1-28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
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
No
IPD Sharing Plan Description
The data presented in this study are available on request from the corresponding author.
Citations:
PubMed Identifier
33723330
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.
Results Reference
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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
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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.
Results Reference
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32890967
Citation
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Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2)

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