NCT04480593

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2 covid19

Timeline
Completed

Started Jun 2020

Shorter than P25 for phase_2 covid19

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 2, 2020

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

July 12, 2020

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 21, 2020

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 30, 2020

Completed
Last Updated

September 30, 2020

Status Verified

September 1, 2020

Enrollment Period

3 months

First QC Date

July 12, 2020

Last Update Submit

September 28, 2020

Conditions

Keywords

PropolisCovid19SARS-CoV-2Anti-inflammatory

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (8)

  • Percentage of participants with adverse events during the use of propolis

    1-28 days

  • Rate and severity of acute kidney injury during the study

    1-28 days

  • Renal replacement therapy.

    1-28 days

  • Rate of need for vasopressor use

    1-28 days

  • Need for intensive care unit (ICU)

    1-28 days

  • +3 more secondary outcomes

Study Arms (3)

Control

ACTIVE COMPARATOR

standard care.

Other: Standard care

EPP-AF 400mg/day

EXPERIMENTAL

Green propolis extract (EPP-AF) at a dose of 400mg / day in addition to the standard treatment.

Drug: Brazilian Green Propolis Extract (EPP-AF)

EPP-AF 800mg/day

EXPERIMENTAL

Green propolis extract (EPP-AF) at a dose of 800mg / day in addition to the standard treatment.

Drug: Brazilian Green Propolis Extract (EPP-AF)

Interventions

Green propolis extract (EPP-AF) administered orally or via nasoenteral tube.

Also known as: Standard care
EPP-AF 400mg/dayEPP-AF 800mg/day

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).

Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Hospitalized patients;
  • Positive RT-PCR for SARS-CoV-2;
  • Years and older.

You may not qualify if:

  • 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;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Sao Rafael

Salvador, Estado de Bahia, 41820340, Brazil

Location

Related Publications (9)

  • 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.

    PMID: 23690844BACKGROUND
  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

COVID-19

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Marcelo Silveira, MD, PhD

    D'Or Institute for Research and Education (IDOR)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
The individual who evaluates the results of interest to the study will not have access to the study steps before the analysis.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: three parallel groups randomly assigned
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 12, 2020

First Posted

July 21, 2020

Study Start

June 2, 2020

Primary Completion

August 30, 2020

Study Completion

August 30, 2020

Last Updated

September 30, 2020

Record last verified: 2020-09

Locations