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

Study Overview
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Brief Summary
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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.

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

Conditions
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Covid19

Intervention / Treatment
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* Drug: Brazilian Green Propolis Extract (EPP-AF)
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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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;

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: three parallel groups randomly assigned
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>standard care. | Other: Standard care<br>* 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).<br>|
| Experimental: EPP-AF 400mg/day<br>Green propolis extract (EPP-AF) at a dose of 400mg / day in addition to the standard treatment. | Drug: Brazilian Green Propolis Extract (EPP-AF)<br>* Green propolis extract (EPP-AF) administered orally or via nasoenteral tube.<br>* Other names: Standard care;|
| Experimental: EPP-AF 800mg/day<br>Green propolis extract (EPP-AF) at a dose of 800mg / day in addition to the standard treatment. | Drug: Brazilian Green Propolis Extract (EPP-AF)<br>* Green propolis extract (EPP-AF) administered orally or via nasoenteral tube.<br>* Other names: Standard care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Need for intensive care unit (ICU) | Assess length of stay in the ICU after randomization in days | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-inflammatory, Propolis, Covid19, SARS-CoV-2