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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Covid19, Inflammation

Intervention / Treatment
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* Drug: Standardized Brazilian Green Propolis Extract
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double-blind, placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* 900mg/day of Placebo for 10 days.<br>|
| Active Comparator: Propolis<br>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<br>* 900mg/day of Standardized Brazilian Green Propolis Extract for 10 days.<br>* Other names: Propolis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Hospitalization time after randomization (in days) | 1-28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Rate and severity of acute kidney injury during the study | Assess the degree of acute kidney injury according to KDIGO. | 1-28 days | 
| Renal replacement therapy. | Assess need or not for renal replacement therapy | 1-28 days | 
| Rate of need for vasopressor use. | Describe the time needed for vasopressors in days after randomization. | 1-28 days | 
| Intensive care unit (ICU) readmission | Rate of readmission to the ICU after randomization | 1-28 days | 
| Invasive oxygenation time | Assess the need for mechanical ventilation in days after randomization. | 1-28 days | 
| Need for Intra-Aortic Balloon Pump | Assess the need for Intra-Aortic Balloon Pump in days after randomization. | 1-28 days | 
| Need for Extracorporeal Oxygenation Membrane (ECMO) | Assess the need for Extracorporeal Oxygenation Membrane in days after randomization. | 1-28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Propolis, Covid19, Anti-Inflammatory Agents, Immunoregulation