Clinical trial NCT04480593: The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19.
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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: Propolis
Covid19
SARS-CoV-2
Anti-inflammatory
Lead sponsor: D'Or Institute for Research and Education
Sponsor class: OTHER
Collaborators: name: Hospital Sao Rafael
First posted: 2020-07-21
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: three parallel groups randomly assigned
Primary purpose: TREATMENT

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.


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;

Primary outcomes:
measure: Composite clinical outcome with oxygen therapy dependency time or hospitalization time
timeFrame: 1-28 days
Secondary outcomes:
measure: Percentage of participants with adverse events during the use of propolis
timeFrame: 1-28 days
measure: Rate and severity of acute kidney injury during the study
timeFrame: 1-28 days
measure: Renal replacement therapy.
timeFrame: 1-28 days
measure: Rate of need for vasopressor use
timeFrame: 1-28 days
measure: Need for intensive care unit (ICU)
timeFrame: 1-28 days
measure: Intensive care unit (ICU) readmission
timeFrame: 1-28 days
measure: Invasive oxygenation time
timeFrame: 1-28 days
measure: Variation of plasma c-reactive protein
timeFrame: 1-7 days
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
state: BA
Study officials:
affiliation: D'Or Institute for Research and Education (IDOR)
name: Marcelo Silveira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.