Page 46 - JCTR-11-3

Journal of Clinical and
Translational Research Greek propolis use in COVID-19: Trial protocol

supplementation. However, these studies differ in extract initiation, and informed consent will be obtained from all
standardization, dosage, and methodological quality, participants.
underscoring the need for rigorously designed clinical
trials using reproducible formulations. 5. Methodology
Historically, propolis has been employed in folk Eligible participants will be adults aged between 18
medicine for wound healing, respiratory infections, and and 85 years, with a confirmed SARS-CoV-2 infection
inflammation, with documented use in Ancient Egypt, as verified through negative reverse transcription
Greece, and China, lending support to its recognized PCR (RT-PCR) testing. Only individuals who are
safety profile. 27,28 In parallel, studies today have provided able to consume oral medications will be considered.
evidence that propolis exhibits numerous antipathogenic Furthermore, participation will require the provision of
and immunoregulatory properties. 29-33 written informed consent.
Given its long-standing use, favorable safety profile, Individuals will be excluded from the study if they
and emerging antiviral evidence, propolis presents as present with severe hepatic or renal impairment, if they
a compelling candidate for integrative approaches to have known hypersensitivity to propolis or alcohol-
COVID-19 management. The extract proposed in this based formulations, or if they are currently enrolled
study is a standardized hydroalcoholic solution derived in another clinical trial. Additional exclusion criteria
from Greek poplar-type propolis, produced under Good include pregnancy or lactation, due to the absence of
Manufacturing Practice conditions. Its chemical profile sufficient safety data regarding the use of propolis in these
has been characterized in previous pharmacognostic populations.
studies and aligns with European Pharmacopeia guidelines Participants in the intervention group will receive
for phenolic content. 800 mg/day of standardized, alcohol-free propolis capsules
This trial is designed to evaluate its potential as an for 10 days. This dosage was selected based on similar
adjunctive therapy to standard care in hospitalized human studies in which doses ranging from 375 mg to
COVID-19 patients, focusing on time to viral clearance, 800 mg/day were found to be safe and well-tolerated. 14,34,35
14
length of hospitalization, symptom severity, and safety In particular, the study by Silveira et al. administered
outcomes. 800 mg/day as an adjunct therapy in hospitalized
COVID-19 patients without observing adverse effects,
3. Objectives supporting the rationale for adopting the same dosage.
The primary objective is to determine whether the Greek The extract will be prepared using ultrasound-assisted
poplar-type propolis extract can accelerate SARS-CoV-2 hydroalcoholic extraction and then spray-dried into a
viral clearance and reduce hospitalization duration when tasteless powder. The placebo arm will receive placebo
used as an adjunct to standard care. Secondary objectives capsules identical in appearance, containing inert starch.
include evaluating changes in body temperature, cough Standard care will be provided in all arms.
severity and duration, cough-specific QoL, safety, and
mortality. 6. Outcome measures
4. Study design 6.1. Primary study outcomes
The primary outcome of this study will assess whether the
This will be a randomized, triple-blind, placebo-controlled, intervention accelerates SARS-CoV-2 viral clearance and
three-arm clinical trial conducted at one or more tertiary- reduces hospitalization duration, compared to placebo and
care hospitals. standard care. Viral shedding will be evaluated through
A total of 441 hospitalized adults aged 18 – 85 with RT-PCR tests using nasopharyngeal swabs, conducted
COVID-19 (polymerase chain reaction [PCR] test- on days 1 (baseline), 5, 7, 10, 14, 15, 16, and 17. Once a
confirmed) will be randomly assigned to receive either negative result is obtained, no further PCR tests will be
(i) standard care plus propolis extract, (ii) standard care performed. These time points were selected based on prior
plus placebo, or (iii) standard care alone. Each group will meta-analyses indicating a SARS-CoV-2 RNA shedding
include 147 participants. duration ranging from 16.8 to 17 days. 36,37

Randomization will be stratified by age and vaccination Hospitalization length will be recorded from the day
status using computer-generated sequences. Investigators, of admission (day 1) to the date of official discharge. This
healthcare providers, and patients will be blinded to outcome is similarly grounded in evidence from recent
treatment allocation. Ethical approval will be sought before meta-analyses reporting a mean hospitalization duration

Volume 11 Issue 3 (2025) 40 doi: 10.36922/jctr.24.00073